银屑病与儿童孤独症的易感基因的突变研究
摘要
一、银屑病患者的FLG基因突变筛查
银屑病(Psoriasis, PS, OMIM 177900)是一种常见的慢性炎症性皮肤病,临床特征为皮肤上出现红斑,并覆有银白色鳞屑,可累及皮肤任何部位,好发于头皮、躯干及四肢伸侧。病理特征为角质增厚或角化不全、颗粒层变薄或消失、棘层增厚；细胞间隙增宽,炎症细胞向表皮和真皮浸润。银屑病在世界范围内发病率约为0.6-4.8%；据估计我国银屑病患者已接近1,000万。银屑病多发病于15岁至30岁之间,常伴随患者一生。银屑病被认为是一种多基因遗传病,其发病机制复杂、至今尚未完全阐明。各种遗传或环境因素主要通过影响免疫系统、炎症反应通路或表皮功能而致病,吸烟、饮酒、精神紧张和物理损伤等其他原因也是常见促发因素。
FLG(filaggrin)基因,位于1q21.3,编码丝聚蛋白(filaggrin, Filament Aggregating Protein)的无活性不溶性前体丝聚蛋白原(profilaggrin)。丝聚蛋白是透明角质颗粒(Keratohyalin Granules,KHG)中的主要成份。丝聚蛋白的终产物在皮肤表面形成保湿因子。FLG基因的突变可导致表皮角化异常,从而引发相关皮肤病。FLG基因最早被证明是寻常性鱼鳞病的致病基因,最近又有报导FLG基因的突变也会导致特异性皮炎的发生。免疫组化的结果显示银屑病患者的表皮颗粒层中丝聚蛋白明显减少,提示FLG基因可能参与了银屑病的发生。
在本研究中,我们收集了2个中国汉族银屑病／鱼鳞病家系,328例中国汉族散发银屑病患者和500例正常对照,采用长片断PCR扩增和直接测序的方法分析患者与正常人的FLG基因序列,寻找与银屑病相关的突变。
我们在家系1中检测到FLG基因的无义突变K4022X,其中先证者携带有纯合突变K4022X,鱼鳞病患者(Ⅰ：4,Ⅱ：6)携带有杂合突变K4022X,另有4个表型正常个体(Ⅰ：2,Ⅱ：1,Ⅱ：4,Ⅱ：5)携带有杂合突变K4022X。在328例散发病人中检测到2个纯合突变K4022X,22个杂合突变K4022X。在500例正常对照中检测到15个杂合突变K4022X。等位基因频率(χ2=12.56,P<0.005)；基因型频率(χ2=16.76,P＜0.005)。Logistic回归中,OR=2.855,95%CIs=2.275-9.974。家系2中我们没有检测到FLG基因的任何突变。
上述研究提示,FLG基因的无义突变K4022X导致银屑病家系1银屑病的发生。银屑病家系2可能存在其它未知基因的突变。FLG基因的K4022X突变在中国汉族人群中的等位基因频率为1.5%,可能是一种皮肤角化异常有关的常见突变。
二、孤独症患者的NLGN3/4/Y基因的突变筛查
孤独症(Autism, OMIM 209850),又称为自闭症,是一种严重的儿童精神发育障碍疾病。通常起病于3岁之前,目前国外报道儿童孤独症的患病率为6%0,国内报道学龄前儿童患病率为1‰,美国约为4-10万,欧洲约10万,中国约2.8-10万男女患病率之比为4：1。主要临床表现为不同程度的社会交往能力缺陷、语言交流技巧障碍、重复刻板的动作和兴趣狭窄等。
孤独症的发病机制至今尚未阐明,已有研究表明,孤独症属于复杂性疾病,且遗传度较高。细胞遗传学研究、同胞、家系研究以及病例对照关联分析、全基因组关联分析等研究已经发现了很多与孤独症相关的位点,克隆了多个易感基因。
研究表明,神经突触异常可能会导致孤独症的发生。NLGN家族属于突触后细胞粘附分子,通过与突触前细胞粘附因子α-neurexin或β-neurexin形成异四聚体,调控神经元的突触兴奋或突触抑制。NLGN家族共包括5个成员：NLGN1 (3q26.31), NLGN2 (17p13.1), NLGN3 (Xq13.1), NLGN4 (Xp22.3)和NLGNY (Yq11.221)。已有研究发现,NLGN3/4/Y的突变可导致孤独症的发生,但在中国人群中还没有NLGN家族基因与孤独症的相关研究。
在本研究中,我们收集了中国汉族人群318例散发孤独症患者及278例正常对照,采用PCR扩增和直接测序的方法分析患者的NLGN3/4/Y基因序列,确定中国孤独症患者的NLGN3/4/Y基因突变。
318例散发孤独症患者中我们检测到NLGN3基因的1个同义突变c.1638G>A和1个错义突变G406S以及NLGN4基因的1个同义突变c.1194C>T和3个错义突变G84R、Q162K、A283T。在278例正常对照中没有发现这6个突变。
NLGN3/4的同义突变c.1638G>A(NLN3)、c.1194C＞T(NLGN4)和错义突变G406S (NLGN3)、G84R (NLGN4)、Q162K (NLGN4)、A283T (NLGN4)有可能会导致孤独症的发生；NLGN3/4基因的突变在不同人群中都可导致孤独症的发生；其他孤独症患者可能存在其它基因的突变。
Chapter 1. Mutation analysis of FLG gene in Chinese Han psoriasis patients
Psoriasis [OMIM 177900] is a common chronic inflammatory dermatosis, clinically characterized by red raised patches covering with white scale on the skin and pathologically characterized by abnormal differentiation in epidermal layers(hyperkeratosis, parakeratosis, stratum granulosum attenuation or disappearance, and acanthosis) and inflammation(intercellular space widen, inflammatory cell infiltration of the dermis and dermal vessel dilatation). By investigating, current prevalence are 0.6-4.8% worldwidely, and 10 million psoriasis patients exist in China. The usual age of onset of psoriasis is between 15 and 30 years and then usually persists for life. Psoriasis is a kind of polygenic disease, and the pathogenesy of psoriasis is so complicated that is still elusive. By affecting immune system, inflammation pathway,the epidermal barrier,various of genetic and environmental factors cause psoriasis. Smoking, drinking, psychentonia and physical injuries and so on are also the triggering factors.
FLG gene, which encodes filaggrin, is located within the epidermal differentiation complex (EDC) on 1q21.3 and expressed late in epidermal differentiation. Keratohyalin granules in the granular layer are predominantly composed of phosphorylated and insoluble protein profilaggrin. Keratohyalin granules in the granular layer are predominantly composed of the phosphorylated and insoluble protein profilaggrin. Loss-of-function FLG mutation leads to abnormal differentiation (hyperkeratosis, parakeratosis) in epidermal layers and cause relative dermatosis。FLG gene is identitied to cause ichthyosis vulgaris first. Resently, it is reported that FLG gene also cause Atopic Dermatitis. Immunohistochemical analysis revealed a markedly reduction of filaggrin expression in psoriatic skin.
2 psoriasis Chinese Han psoriasis/ ichthyosis vulgaris families,328 sporadic unrelated Chinese Han patients with psoriasis and 500 controls were involved in our study. By long range PCR and direct sequencing we analyze the FLG gene of the psoriasis patients and the health individuals,
we identified a nonsense mutation, K4022X, in the family 1. The proband(Ⅲ:2) carries homozygous nonsense mutation, K4022X. TheⅣpatients (Ⅰ:4,Ⅱ:6)carry heterozygous nonsense mutation, K4022X. Besides, four health members (Ⅰ:2,Ⅱ:1,Ⅱ:4,Ⅱ:5)carry heterozygous nonsense mutation, K4022X. We identified 2 of 328 cases carry homozygous nonsense mutation, K4022X, and 22 of 328 cases carry heterozygous nonsense mutation, K4022X. We identified 15 of 500 controls carry heterozygous nonsense mutation, K4022X. By statistical analysis, we obtain allele frequencies:χ2=12.56,ν=1, P<0.005; genotype frequencies:χ2=16.76,ν=2, P<0.005; the OR(odds ratio)=2.855,95% CIs(Confidence Intervals)=2.275-9.974. We did not found any FLG mutation in the family 2.
According to the studies aboved, the nonsense mutation, K4022X, may lead to the onset of the psoriasis in the family 1. May any other gene mutation exists in the family 2 to cause psoriasis. The allele frequency of the nonsense mutation, K4022X, is 1.5% in Chinese Han People. K4022X is a kind of common FLG mutation related to abnormal differentiation in epidermal layers.
Chapter 2. Mutation analysis of NLGN3/4/Y gene in Chinese Han autism patients
Autism [OMIM 209850] is a severe childhood neurodevelopmental disorder. The onset of autism is before 3 years of age. The prevalence reported is increasing year by year. By investigating, current prevalence are 0.6% worldwidely and 0.1% in China. Males are affected by autism approximately 4 times more frequently than females. The main clinical character is impairment of social and communication skills, repetitive and stereotypical behaviors, restricted range of interests.
The etiology of autism is still unknown. However, by investigating, autism is a complex disease with high heritability. Cytogenetics study showed that it has a high incidence of chromosome abnormality. Many related loci and several predisposing genes have been identified by sibling, family study, case-control association study, Genome-wide association study(GWAS) and so on.
It is demonstrated that the abnormal neuronal synapse is related to autism. Neuroligins are postsynaptic cell adhesion molecules, by forming heterotetramer with presynaptic cell adhesion molecules neurexins, regulate the fine balance between excitation and inhibition of the synapse. In humans, the neuroligin protein family comtain five genes, NLGN1,2, 3,4 and 4Y. It is reported the NLGN3/4 mutations cause autism. However, no study on NLGNs and autism have done in Chinese Han people.
318 sporadic unrelated Chinese Han patients with autism were involved in our study. By routine PCR and direct sequencing we analyze the NLGN3/4/Y genes of the autism patients.
we identified a samesense mutation c.1638G>A and 1 missense mutations G406S in NLGN3 and a samesense mutation c.1194C>T and 3 missense mutations G84R、Q162K and A283T in NLGN4. All the 6 mutations have not been identified in 278 controls.
These mutations in NLGN3/4 may cause autism. The NLGN3/4 mutations can cause autism in different race of people. Maybe other gene mutations exist in the patients.
银屑病(Psoriasis, PS, OMIM 177900)是一种常见的慢性炎症性皮肤病,临床特征为皮肤上出现红斑,并覆有银白色鳞屑,可累及皮肤任何部位,好发于头皮、躯干及四肢伸侧。病理特征为角质增厚或角化不全、颗粒层变薄或消失、棘层增厚；细胞间隙增宽,炎症细胞向表皮和真皮浸润。银屑病在世界范围内发病率约为0.6-4.8%；据估计我国银屑病患者已接近1,000万。银屑病多发病于15岁至30岁之间,常伴随患者一生。银屑病被认为是一种多基因遗传病,其发病机制复杂、至今尚未完全阐明。各种遗传或环境因素主要通过影响免疫系统、炎症反应通路或表皮功能而致病,吸烟、饮酒、精神紧张和物理损伤等其他原因也是常见促发因素。
FLG(filaggrin)基因,位于1q21.3,编码丝聚蛋白(filaggrin, Filament Aggregating Protein)的无活性不溶性前体丝聚蛋白原(profilaggrin)。丝聚蛋白是透明角质颗粒(Keratohyalin Granules,KHG)中的主要成份。丝聚蛋白的终产物在皮肤表面形成保湿因子。FLG基因的突变可导致表皮角化异常,从而引发相关皮肤病。FLG基因最早被证明是寻常性鱼鳞病的致病基因,最近又有报导FLG基因的突变也会导致特异性皮炎的发生。免疫组化的结果显示银屑病患者的表皮颗粒层中丝聚蛋白明显减少,提示FLG基因可能参与了银屑病的发生。
在本研究中,我们收集了2个中国汉族银屑病／鱼鳞病家系,328例中国汉族散发银屑病患者和500例正常对照,采用长片断PCR扩增和直接测序的方法分析患者与正常人的FLG基因序列,寻找与银屑病相关的突变。
我们在家系1中检测到FLG基因的无义突变K4022X,其中先证者携带有纯合突变K4022X,鱼鳞病患者(Ⅰ：4,Ⅱ：6)携带有杂合突变K4022X,另有4个表型正常个体(Ⅰ：2,Ⅱ：1,Ⅱ：4,Ⅱ：5)携带有杂合突变K4022X。在328例散发病人中检测到2个纯合突变K4022X,22个杂合突变K4022X。在500例正常对照中检测到15个杂合突变K4022X。等位基因频率(χ2=12.56,P<0.005)；基因型频率(χ2=16.76,P＜0.005)。Logistic回归中,OR=2.855,95%CIs=2.275-9.974。家系2中我们没有检测到FLG基因的任何突变。
上述研究提示,FLG基因的无义突变K4022X导致银屑病家系1银屑病的发生。银屑病家系2可能存在其它未知基因的突变。FLG基因的K4022X突变在中国汉族人群中的等位基因频率为1.5%,可能是一种皮肤角化异常有关的常见突变。
二、孤独症患者的NLGN3/4/Y基因的突变筛查
孤独症(Autism, OMIM 209850),又称为自闭症,是一种严重的儿童精神发育障碍疾病。通常起病于3岁之前,目前国外报道儿童孤独症的患病率为6%0,国内报道学龄前儿童患病率为1‰,美国约为4-10万,欧洲约10万,中国约2.8-10万男女患病率之比为4：1。主要临床表现为不同程度的社会交往能力缺陷、语言交流技巧障碍、重复刻板的动作和兴趣狭窄等。
孤独症的发病机制至今尚未阐明,已有研究表明,孤独症属于复杂性疾病,且遗传度较高。细胞遗传学研究、同胞、家系研究以及病例对照关联分析、全基因组关联分析等研究已经发现了很多与孤独症相关的位点,克隆了多个易感基因。
研究表明,神经突触异常可能会导致孤独症的发生。NLGN家族属于突触后细胞粘附分子,通过与突触前细胞粘附因子α-neurexin或β-neurexin形成异四聚体,调控神经元的突触兴奋或突触抑制。NLGN家族共包括5个成员：NLGN1 (3q26.31), NLGN2 (17p13.1), NLGN3 (Xq13.1), NLGN4 (Xp22.3)和NLGNY (Yq11.221)。已有研究发现,NLGN3/4/Y的突变可导致孤独症的发生,但在中国人群中还没有NLGN家族基因与孤独症的相关研究。
在本研究中,我们收集了中国汉族人群318例散发孤独症患者及278例正常对照,采用PCR扩增和直接测序的方法分析患者的NLGN3/4/Y基因序列,确定中国孤独症患者的NLGN3/4/Y基因突变。
318例散发孤独症患者中我们检测到NLGN3基因的1个同义突变c.1638G>A和1个错义突变G406S以及NLGN4基因的1个同义突变c.1194C>T和3个错义突变G84R、Q162K、A283T。在278例正常对照中没有发现这6个突变。
NLGN3/4的同义突变c.1638G>A(NLN3)、c.1194C＞T(NLGN4)和错义突变G406S (NLGN3)、G84R (NLGN4)、Q162K (NLGN4)、A283T (NLGN4)有可能会导致孤独症的发生；NLGN3/4基因的突变在不同人群中都可导致孤独症的发生；其他孤独症患者可能存在其它基因的突变。
Chapter 1. Mutation analysis of FLG gene in Chinese Han psoriasis patients
Psoriasis [OMIM 177900] is a common chronic inflammatory dermatosis, clinically characterized by red raised patches covering with white scale on the skin and pathologically characterized by abnormal differentiation in epidermal layers(hyperkeratosis, parakeratosis, stratum granulosum attenuation or disappearance, and acanthosis) and inflammation(intercellular space widen, inflammatory cell infiltration of the dermis and dermal vessel dilatation). By investigating, current prevalence are 0.6-4.8% worldwidely, and 10 million psoriasis patients exist in China. The usual age of onset of psoriasis is between 15 and 30 years and then usually persists for life. Psoriasis is a kind of polygenic disease, and the pathogenesy of psoriasis is so complicated that is still elusive. By affecting immune system, inflammation pathway,the epidermal barrier,various of genetic and environmental factors cause psoriasis. Smoking, drinking, psychentonia and physical injuries and so on are also the triggering factors.
FLG gene, which encodes filaggrin, is located within the epidermal differentiation complex (EDC) on 1q21.3 and expressed late in epidermal differentiation. Keratohyalin granules in the granular layer are predominantly composed of phosphorylated and insoluble protein profilaggrin. Keratohyalin granules in the granular layer are predominantly composed of the phosphorylated and insoluble protein profilaggrin. Loss-of-function FLG mutation leads to abnormal differentiation (hyperkeratosis, parakeratosis) in epidermal layers and cause relative dermatosis。FLG gene is identitied to cause ichthyosis vulgaris first. Resently, it is reported that FLG gene also cause Atopic Dermatitis. Immunohistochemical analysis revealed a markedly reduction of filaggrin expression in psoriatic skin.
2 psoriasis Chinese Han psoriasis/ ichthyosis vulgaris families,328 sporadic unrelated Chinese Han patients with psoriasis and 500 controls were involved in our study. By long range PCR and direct sequencing we analyze the FLG gene of the psoriasis patients and the health individuals,
we identified a nonsense mutation, K4022X, in the family 1. The proband(Ⅲ:2) carries homozygous nonsense mutation, K4022X. TheⅣpatients (Ⅰ:4,Ⅱ:6)carry heterozygous nonsense mutation, K4022X. Besides, four health members (Ⅰ:2,Ⅱ:1,Ⅱ:4,Ⅱ:5)carry heterozygous nonsense mutation, K4022X. We identified 2 of 328 cases carry homozygous nonsense mutation, K4022X, and 22 of 328 cases carry heterozygous nonsense mutation, K4022X. We identified 15 of 500 controls carry heterozygous nonsense mutation, K4022X. By statistical analysis, we obtain allele frequencies:χ2=12.56,ν=1, P<0.005; genotype frequencies:χ2=16.76,ν=2, P<0.005; the OR(odds ratio)=2.855,95% CIs(Confidence Intervals)=2.275-9.974. We did not found any FLG mutation in the family 2.
According to the studies aboved, the nonsense mutation, K4022X, may lead to the onset of the psoriasis in the family 1. May any other gene mutation exists in the family 2 to cause psoriasis. The allele frequency of the nonsense mutation, K4022X, is 1.5% in Chinese Han People. K4022X is a kind of common FLG mutation related to abnormal differentiation in epidermal layers.
Chapter 2. Mutation analysis of NLGN3/4/Y gene in Chinese Han autism patients
Autism [OMIM 209850] is a severe childhood neurodevelopmental disorder. The onset of autism is before 3 years of age. The prevalence reported is increasing year by year. By investigating, current prevalence are 0.6% worldwidely and 0.1% in China. Males are affected by autism approximately 4 times more frequently than females. The main clinical character is impairment of social and communication skills, repetitive and stereotypical behaviors, restricted range of interests.
The etiology of autism is still unknown. However, by investigating, autism is a complex disease with high heritability. Cytogenetics study showed that it has a high incidence of chromosome abnormality. Many related loci and several predisposing genes have been identified by sibling, family study, case-control association study, Genome-wide association study(GWAS) and so on.
It is demonstrated that the abnormal neuronal synapse is related to autism. Neuroligins are postsynaptic cell adhesion molecules, by forming heterotetramer with presynaptic cell adhesion molecules neurexins, regulate the fine balance between excitation and inhibition of the synapse. In humans, the neuroligin protein family comtain five genes, NLGN1,2, 3,4 and 4Y. It is reported the NLGN3/4 mutations cause autism. However, no study on NLGNs and autism have done in Chinese Han people.
318 sporadic unrelated Chinese Han patients with autism were involved in our study. By routine PCR and direct sequencing we analyze the NLGN3/4/Y genes of the autism patients.
we identified a samesense mutation c.1638G>A and 1 missense mutations G406S in NLGN3 and a samesense mutation c.1194C>T and 3 missense mutations G84R、Q162K and A283T in NLGN4. All the 6 mutations have not been identified in 278 controls.
These mutations in NLGN3/4 may cause autism. The NLGN3/4 mutations can cause autism in different race of people. Maybe other gene mutations exist in the patients.
引文
[1]杨曙光,胡月璋,韩允.儿童孤独症的流行病学调查分析.实用儿科临床杂志,2007,24(
[2]Lebwohl M. Psoriasis. Lancet,2003,361(8.
[3]刘刁骋.银屑病发病机制的研究进展.沈阳医学院学报,2007,9(1008-2344(2007)04-0248-03)：
[4]Bouwstra J.A.Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta,2006,1758(12):2080-2095.
[5]Farber E.M., Nall M.L.Watson W. Natural history of psoriasis in 61 twin pairs. Arch Dermatol,1974,109(2):207-211.
[6]Brandrup F., Green A.Holm N. [Occurrence of psoriasis in Denmark]. Ugeskr Laeger,1982,144(47):3538-3541.
[7]Farber E.M.Nall M.L. The natural history of psoriasis in 5,600 patients. Dermatologica,1974,148(1):1-18.
[8]Asumalahti K., Ameen M., Suomela S., et al. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol, 2003,120(4):627-632.
[9]Capon F H.C., Veal CD, Tillman D, Burden AD, Barker JN, Bowcock AM, Trembath RC. Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis. J Med Genet,2004, 41(6)(60.
[10]Matthews D F.L., Powles A, Weber J, McCarthy M, Fisher E, Davies K, Williamson R. Evidence that a locus for familial psoriasis maps to chromosome 4q. Nat Genet,1998,14(2)(3.
[11]Capon F., Novelli G, Semprini S., et al. Searching for psoriasis susceptibility genes in Italy:genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol,1999,112(1):32-35.
[12]Enlund F., Samuelsson L., Enerback C., et al. Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden. Eur J Hum Genet,1999,7(7):783-790.
[13]Lee Y.A., Ruschendorf F., Windemuth C., et al. Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13. Am J Hum Genet,2000,67(4):1020-1024.
[14]Parham C C.M., Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbetal and a novel cytokine receptor subunit, IL-23R J Immunol,2002, 168(11)(10.
[15]Nair R.P., Henseler T., Jenisch S., et al. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan Hum Mol Genet,1997,6(8):1349-1356.
[16]Zhang XJ H.P., Wang ZX, Zhang J, Li YB, Wang HY, Wei SC, Chen SY, Xu SJ, Jin L, Yang S, Huang W. Evidence for a major psoriasis susceptibility locus at 6p21(PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese hans. J Invest Dermatol.,2002,119(6)(6.
[17]Asumalahti K., Laitinen, T., Lahermo, P., Suomela, S., Itkonen-Vatjus, R., Jansen, C., Karvonen, J., Karvonen, S.-L., Reunala, T., Snellman, E., Uurasmaa, T., Saarialho-Kere, U., Kere, J. Psoriasis susceptibility locus on 18p revealed by genome scan in Finnish families not associated with PSORS1. J. Invest. Derm, 2003,121(6.
[18]Cargill M., Schrodi, S. J., Chang, M., Garcia, V. E., Brandon, R., Callis, K. P., Matsunami, N., Ardlie, K. G, Civello, D., Catanese, J. J., Leong, D. U., Panko, J. M., McAllister, L. B., Hansen, C. B., Papenfuss, J., Prescott, S. M., White, T. J., Leppert, M. F., Krueger, G. G., Begovich, A. B. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet,2007,80(117.
[19]Capon F B.M., Wolf N, Quaranta M, Huffmeier U, Allen M, Timms K, Abkevich V, Gutin A, Smith R, Warren RB, Young HS, Worthington J, Burden AD, Griffiths CE, Hayday A, Nestle FO, Reis A, Lanchbury J, Barker JN, Trembath RC. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet,2008,17(13)(45):1938.
[20]Rebala K., Szczerkowska-Dobosz A., Niespodziana K., et al. Simple and rapid screening for HLA-Cw*06 in Polish patients with psoriasis. Clin Exp Dermatol, 2009,
[21]Zhang X.J. [Enlightenment from genome-wide association study to genetics of psoriasis]. Zhejiang Da Xue Xue Bao Yi Xue Ban,2009,38(4):333-337.
[22]Nair R.P., Duffin K.C., Helms C., et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet,2009,41(2):199-204.
[23]Huffmeier U B.J., Becker T, Armour JA, Traupe H, Estivill X, Riveira-Munoz E, Mossner R, Reich K, Kurrat W, Wienker TF, Schalkwijk J, Zeeuwen PL, Reis A.Institute of Human Genetics U.H.E., University Erlangen-Nuremberg, Erlangen, Germany. Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. J Invest Dermatol,2010,130(4)(6.
[24]Giardina E., Capon F., De Rosa M.C., et al. Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus. Ann Hum Genet,2004,68(Pt 6):639-645.
[25]Chen H., Toh T.K., Szeverenyi I., et al. Association of skin barrier genes within the PSORS4 locus is enriched in Singaporean Chinese with early-onset psoriasis. J Invest Dermatol,2009,129(3):606-614.
[26]Zhang XJ H.W., Yang S, Sun LD, Zhang FY, Zhu QX, Zhang FR, Zhang C, Du WH, Pu XM, Li H, Xiao FL, Wang ZX, Cui Y, Hao F, Zheng J, Yang XQ, Cheng H, He CD, Liu XM, Xu LM, Zheng HF, Zhang SM, Zhang JZ, Wang HY, Cheng YL, Ji BH, Fang QY, Li YZ, Zhou FS, Han JW, Quan C, Chen B, Liu JL, Lin D, Fan L, Zhang AP, Liu SX, Yang CJ, Wang PG, Zhou WM, Lin GS, Wu WD, Fan X, Gao M, Yang BQ, Lu WS, Zhang Z, Zhu KJ, Shen SK, Li M, Zhang XY, Cao TT, Ren W, Zhang X, He J, Tang XF, Lu S, Yang JQ, Zhang L, Wang DN, Yuan F, Yin XY, Huang HJ, Wang HF, Lin XY, Liu JJ. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet,2009,41(2):205-210.
[27]de Cid R R.-M.E., Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramis G, Ballana E, Martin-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I, Eichler EE, Lazaro C, Pujol RM, Armengol L, Abecasis G, Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet,2009,41(2):211-215.
[28]Hoffjan S.Stemmler S. On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. Br J Dermatol,2007,157(3): 441-449.
[29]de Guzman Strong C., Conlan S., Deming C.B., et al. A milieu of regulatory elements in the epidermal differentiation complex syntenic block:implications for atopic dermatitis and psoriasis. Hum Mol Genet,2010,19(8):1453-1460.
[30]Mischke D K.B., Marenholz I, Volz A, Ziegler A. Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. J Invest Dermatol,1996,106(5):989-992.
[31]Gan S.Q., McBride O.W., Idler W.W., et al. Organization, structure, and polymorphisms of the human profilaggrin gene. Biochemistry,1991,30(23): 5814.
[32]Markova NG M.L., Chipev CC, Gan SQ, Idler WW, Steinert PM. Profilaggrin is a major epidermal calcium-binding protein. Mol Cell Biol,1993,13(1)(613-625.
[33]Smith F.J., Irvine A.D., Terron-Kwiatkowski A., et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet,2006,38(3): 337-342.
[34]Presland R.B., Boggess D., Lewis S.P., et al. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice:an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol,2000,115(6):1072-1081.
[35]Huffmeier U T.H., Oji V, Lascorz J, Stander M, Lohmann J, Wendler J, Burkhardt H, Reis A. Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients. J Invest Dermatol,2007,127(6)(1367-1370.
[36]Chang YC W.W., Chen CH, Hu CF, Hsu LA. Association between P478S polymorphism of the filaggrin gene and risk of psoriasis in a Chinese population in Taiwan. Arch Dermatol Res,2008,300(3)(7.
[37]Sambrook J R.D. Molecular Cloning:A Laboratry Manual(分子克隆实验指南,黄培堂等译).2002,463-471.
[38]Sandilands A., Terron-Kwiatkowski A., Hull P.R., et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema Nat Genet,2007,39(5):650-654.
[39]Nomura T., Sandilands A., Akiyama M., et al. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol,2007,119(2):434-440.
[40]Nemoto-Hasebe I., Akiyama M., Nomura T., et al. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema Br J Dermatol,2009,161(6):1387-1390.
[41]Fallon P.G., Sasaki T., Sandilands A., et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet,2009,41(5):602-608.
[42]Scharschmidt T.C., Man M.Q., Hatano Y., et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol,2009,124(3):496-506,506 e491-496.
[43]Palmer C.N., Irvine A.D., Terron-Kwiatkowski A., et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet,2006,38(4):441-446.
[44]Liao H., Waters A.J., Goudie D.R., et al. Filaggrin Mutations Are Genetic Modifying Factors Exacerbating X-Linked Ichthyosis. J Invest Dermatol,2007,
[45]Walley A.J., Chavanas S., Moffatt M.F., et al. Gene polymorphism in Netherton and common atopic disease. Nat Genet,2001,29(2):175-178.
[46]Vasilopoulos Y., Cork M.J., Murphy R., et al. Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis. J Invest Dermatol,2004,123(1):62-66.
[47]Kanner L. Follow-up study of eleven autistic children originally reported in 1943. J Autism Child Schizophr,1971,1(2):119-145.
[48]Lainhart J.E., Ozonoff S., Coon H., et al. Autism, regression, and the broader autism phenotype. Am J Med Genet,2002,113(3):231-237.
[49]Sutcliffe J.S. Genetics. Insights into the pathogenesis of autism. Science,2008, 321(5886):208-209.
[50]Bailey A., Le Couteur A., Gottesman I., et al. Autism as a strongly genetic disorder:evidence from a British twin study. Psychol Med,1995,25(1):63-77.
[51]Szatmari P., Jones M.B., Zwaigenbaum L., et al. Genetics of autism:overview and new directions. J Autism Dev Disord,1998,28(5):351-368.
[52]Rutter M. Genetic studies of autism:from the 1970s into the millennium. J Abnorm Child Psychol,2000,28(1):3-14.
[53]Bartlett C.W., Goedken R.Vieland V.J. Effects of updating linkage evidence across subsets of data:reanalysis of the autism genetic resource exchange data set Am J Hum Genet,2005,76(4):688-695.
[54]Maussion G, Carayol J., Lepagnol-Bestel A.M., et al. Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism. Hum Mol Genet,2008,17(16):2541-2551.
[55]Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum Mol Genet,2001,10(9):973-982.
[56]Buxbaum J.D., Silverman J.M., Smith C.J., et al. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. Am J Hum Genet,2001,68(6):1514-1520.
[57]A genomewide screen for autism:strong evidence for linkage to chromosomes 2q,7q, and 16p. Am J Hum Genet,2001,69(3):570-581.
[58]Auranen M., Vanhala R., Varilo T., et al. A genomewide screen for autism-spectrum disorders:evidence for a major susceptibility locus on chromosome 3q25-27. Am J Hum Genet,2002,71(4):777-790.
[59]Yu C.E., Dawson G, Munson J., et al. Presence of large deletions in kindreds with autism. Am J Hum Genet,2002,71(1):100-115.
[60]Trikalinos T.A., Karvouni A., Zintzaras E., et al. A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol Psychiatry,2006,11(1): 29-36.
[61]A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium. Hum Mol Genet,1998,7(3):571-578.
[62]Alarcon M., Cantor R.M., Liu J., et al. Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families. Am J Hum Genet,2002, 70(1):60-71.
[63]Molloy C.A., Keddache M.Martin L.J. Evidence for linkage on 21q and 7q in a subset of autism characterized by developmental regression. Mol Psychiatry, 2005,10(8):741-746.
[64]Ma D.Q., Cuccaro M.L., Jaworski J.M., et al. Dissecting the locus heterogeneity of autism:significant linkage to chromosome 12q14. Mol Psychiatry,2007,12(4): 376-384.
[65]Ritvo E.R., Mason-Brothers A., Menkes J.H., et al. Association of autism, retinoblastoma, and reduced esterase D activity. Arch Gen Psychiatry,1988, 45(6):600.
[66]Bradford Y., Haines J., Hutcheson H., et al. Incorporating language phenotypes strengthens evidence of linkage to autism. Am J Med Genet,2001,105(6): 539-547.
[67]Clayton-Smith J., Webb T., Cheng X.J., et al. Duplication of chromosome 15 in the region 15q11-13 in a patient with developmental delay and ataxia with similarities to Angelman syndrome. J Med Genet,1993,30(6):529-531.
[68]Bundey S., Hardy C., Vickers S., et al. Duplication of the 15q11-13 region in a patient with autism, epilepsy and ataxia Dev Med Child Neurol,1994,36(8): 736-742.
[69]Hernando C., Plaja A., Rigola M.A., et al. Comparative genomic hybridisation shows a partial de novo deletion 16p11.2 in a neonate with multiple congenital malformations. J Med Genet,2002,39(5):E24.
[70]Shimojima K., Inoue T., Fujii Y., et al. A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and hemivertebrae. Eur J Med Genet, 2009,52(6):433-435.
[71]Yonan A.L., Alarcon M., Cheng R., et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet,2003,73(4):886-897.
[72]Stone J.L., Merriman B., Cantor R.M., et al. Evidence for sex-specific risk alleles in autism spectrum disorder. Am J Hum Genet,2004,75(6):1117-1123.
[73]Cantor R.M., Kono N., Duvall J.A., et al. Replication of autism linkage: fine-mapping peak at 17q21. Am J Hum Genet,2005,76(6):1050-1056.
[74]Thomas N.S., Sharp A.J., Browne C.E., et al. Xp deletions associated with autism in three females. Hum Genet,1999,104(1):43-48.
[75]Jamain S., Quach H., Betancur C., et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet, 2003,34(1):27-29.
[76]Lam C.W., Yeung W.L., Ko C.H., et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet,2000, 37(12):E41.
[77]Herault J., Petit E., Martineau J., et al. Autism and genetics:clinical approach and association study with two markers of HRAS gene. Am J Med Genet,1995, 60(4):276-281.
[78]Comings D.E., Wu S., Chiu C., et al. Studies of the c-Harvey-Ras gene in psychiatric disorders. Psychiatry Res,1996,63(1):25-32.
[79]Kim S J., Brune C.W., Kistner E.O., et al. Transmission disequilibrium testing of the chromosome 15q11-q13 region in autism. Am J Med Genet B Neuropsychiatr Genet,2008,147B(7):1116-1125.
[80]Jacob S., Landeros-Weisenberger A.Leckman J.F. Autism spectrum and obsessive-compulsive disorders:OC behaviors, phenotypes and genetics. Autism Res,2009,2(6):293-311.
[81]Cook E.H., Jr.Scherer S.W. Copy-number variations associated with neuropsychiatric conditions. Nature,2008,455(7215):919-923.
[82]Golimbet V.E.Koren E.V. [Copy number variations in the human genome-a new page in psychiatric genetics:the collaborative project PsychCNV's]. Zh Nevrol Psikhiatr Im S S Korsakova,2010,110(1):107-109.
[83]Sebat J., Lakshmi B., Malhotra D., et al. Strong association of de novo copy number mutations with autism. Science,2007,316(5823):445-449.
[84]Kusenda M. Sebat J. The role of rare structural variants in the genetics of autism spectrum disorders. Cytogenet Genome Res,2008,123(1-4):36-43.
[85]Zhao X., Pak C., Smrt R.D., et al. Epigenetics and Neural developmental disorders:Washington DC, September 18 and 19,2006. Epigenetics,2007,2(2): 126-134.
[86]Gonzales M.L.LaSalle J.M. The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep,2010,12(2):127-134.
[87]Currenti S.A. Understanding and determining the etiology of autism. Cell Mol Neurobiol,2010,30(2):161-171.
[88]Scheiffele P., Fan J., Choih J., et al. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell,2000,101(6): 657-669.
[89]Ichtchenko K., Nguyen T.Sudhof T.C. Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem,1996,271(5):2676-2682.
[90]Ichtchenko K., Hata Y., Nguyen T., et al. Neuroligin 1:a splice site-specific ligand for beta-neurexins. Cell,1995,81(3):435-443.
[91]Laumonnier F., Bonnet-Brilhault F., Gomot M., et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet,2004,74(3):552-557.
[92]Ylisaukko-oja T., Alarcon M., Cantor R.M., et al. Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families. Ann Neurol,2006,59(1):145-155.
[93]Blasi F., Bacchelli E., Pesaresi G, et al. Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am J Med Genet B Neuropsychiatr Genet,2006,141B(3): 220-221.
[94]Talebizadeh Z., Bittel D.C., Veatch O.J., et al. Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism? J Autism Dev Disord,2004,34(6): 735-736.
[95]Yan J., Feng J., Schroer R., et al. Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr Genet,2008,18(4):204-207.
[96]Koehnke J., Jin X., Budreck E.C., et al. Crystal structure of the extracellular cholinesterase-like domain from neuroligin-2. Proc Natl Acad Sci USA,2008, 105(6):1873-1878.
[97]Rao A., Harms K.J.Craig A.M. Neuroligation:building synapses around the neurexin-neuroligin link. Nat Neurosci,2000,3(8):747-749.
[98]Dean C., Scholl F.G., Choih J., et al. Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci,2003,6(7):708-716.
[99]Tabuchi K., Blundell J., Etherton M.R., et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science,2007, 318(5847):71-76.
[100]Jamain S., Radyushkin K., Hammerschmidt K., et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci USA,2008,105(5):1710-1715.
[1]McGrath JA U.J. The filaggrin story:novel insights into skin-barrier function and disease. Trends Mol Med,2008,14(1)(20-27.
[2]Bouwstra J.A.Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta,2006,1758(12):2080-2095.
[3]Volz A., Korge B.P., Compton J.G., et al. Physical mapping of a functional cluster of epidermal differentiation genes on chromosome 1q21. Genomics,1993, 18(1):92-99.
[4]Shwayder T.Akland T. Neonatal skin barrier:structure, function, and disorders. Dermatol Ther,2005,18(2):87-103.
[5]McKinley-Grant L.J., Idler W.W., Bernstein I.A., et al. Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21. Proc Natl Acad Sci USA,1989,86(13):4848-4852.
[6]Presland R.B., Haydock P.V., Fleckman P., et al. Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. J Biol Chem,1992, 267(33):23772-23781.
[7]Gan S.Q., McBride O.W., Idler W.W., et al. Organization, structure, and polymorphisms of the human profilaggrin gene. Biochemistry,1991,30(23): 5814.
[8]Markova NG M.L., Chipev CC, Gan SQ, Idler WW, Steinert PM. Profilaggrin is a major epidermal calcium-binding protein Mol Cell Biol,1993,13(1)(613-625.
[9]Jang SI S.P., Markova NG. Activator protein 1 activity is involved in the regulation of the cell type-specific expression from the proximal promoter of the human profilaggrin gene. J Biol Chem,1996,271(39)(24105-24114.
[10]Jang SI K.-J.N., Morasso MI, Steinert PM, Markova NG. Complex interactions between epidermal POU domain and activator protein 1 transcription factors regulate the expression of the profilaggrin gene in normal human epidermal keratinocytes. J Biol Chem,2000,275(20)(15295-15304.
[11]King KE P.R., Gerdes MJ, Tokino T, Yamashita T, Baker CC, Weinberg WC. Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis. Carcinogenesis,2006,27(1)(53-63.
[12]Candi E R.A., Terrinoni A, Giamboi-Miraglia A, Lena AM, Mantovani R, Knight R, Melino G. DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci U S A,2007, 104(29)(11999-12004.
[13]Park GT M.M. Regulation of the Dlx3 homeobox gene upon differentiation of mouse keratinocytes. J Biol Chem,1999,274(37)(26599-26608.
[14]Icre G, Wahli W.Michalik L. Functions of the peroxisome proliferator-activated receptor (PPAR) alpha and beta in skin homeostasis, epithelial repair, and morphogenesis. J Investig Dermatol Symp Proc,2006,11(1):30-35.
[15]Mao-Qiang M., Fowler A.J., Schmuth M., et al. Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation. J Invest Dermatol,2004,123(2):305-312.
[16]Presland R.B., Tomic-Canic M., Lewis S.P., et al. Regulation of human profilaggrin promoter activity in cultured epithelial cells by retinoic acid and glucocorticoids. J Dermatol Sci,2001,27(3):192-205.
[17]Presland R.B., Bassuk J.A., Kimball J.R., et al. Characterization of two distinct calcium-binding sites in the amino-terminus of human profilaggrin. J Invest Dermatol,1995,104(2):218-223.
[18]Laster A.J.Haynes B.F. Characterization of a monoclonal antibody, RTE-21, that binds to keratohyalin granule-associated proteins in epithelial cells of human skin and thymus. Clin Immunol Immunopathol,1986,41(1):130-144.
[19]Presland R.B., Kimball J.R., Kautsky M.B., et al. Evidence for specific proteolytic cleavage of the N-terminal domain of human profilaggrin during epidermal differentiation. J Invest Dermatol,1997,108(2):170-178.
[20]Kam E R.K., Lim SK, Dale BA. Identification of rat epidermal profilaggrin phosphatase as a member of the protein phosphatase 2A family. J Cell Sci,1993, 106(8.
[21]Tarcsa E., Marekov L.N., Mei G., et al. Protein unfolding by peptidylarginine deiminase. Substrate specificity and structural relationships of the natural substrates trichohyalin and filaggrin. J Biol Chem,1996,271(48):30709-30716.
[22]Mechin MC E.M., Nachat R, Chavanas S, Charveron M, Ishida-Yamamoto A, Serre G, Takahara H, Simon M. The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations. Cell Mol Life Sci,2005,62(17)(12.
[23]Denecker G, Hoste E., Gilbert B., et al. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat Cell Biol,2007,9(6):666-674.
[24]Denecker G, Ovaere P., Vandenabeele P., et al. Caspase-14 reveals its secrets. J Cell Biol,2008,180(3):451-458.
[25]Kamata Y., Taniguchi A., Yamamoto M., et al. Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids. J Biol Chem,2009,284(19):12829-12836.
[26]Rawlings A.V.Harding C.R. Moisturization and skin barrier function. Dermatol Ther,2004,17 Suppl 1(43-48.
[27]Presland R.B., Boggess D., Lewis S.P., et al. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice:an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol,2000,115(6):1072-1081.
[28]Schwartz D.R., Homanics G.E., Hoyt D.G., et al. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci USA,1999,96(8):4680-4685.
[29]Suchi M., Harada N., Wada Y, et al. Molecular cloning of a cDNA encoding human histidase. Biochim Biophys Acta,1993,1216(2):293-295.
[30]CR S.I.H. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol,1986,115(84-92.
[31]Katagiri C S., J., Nomura, J. and Denda, M. Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice. J. Dermatol Sci,2003,31(29-35.
[32]Wells R.S., Kerr CB. Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. Br Med J,1966,1(947-950.
[33]Lei G, Zhang YY H. Investigation on the prevalence of Ichthyosis in Sichuan province. Chin J Dermatol (in Chinese),1992,25(105-106.
[34]雷光鲁张.,胡应.四川省鱼鳞病流行病学调查报告.中华皮肤科杂志,1992,25(105-106.
[35]Sybert V.P., Dale B.A.Holbrook K.A. Ichthyosis vulgaris:identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. J Invest Dermatol,1985,84(3):191-194.
[36]Nirunsuksiri W P.R., Brumbaugh SG, Dale BA, Fleckman P. Decreased profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control. J Biol Chem,1995,270(6.
[37]Nirunsuksiri W., Zhang S.H.Fleckman P. Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with ichthyosis vulgaris. J Invest Dermatol,1998,110(6):854-861.
[38]Compton J.G., DiGiovanna J.J., Johnston K.A., et al. Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1. Exp Dermatol,2002,11(6):518-526.
[39]Zhong W., Cui B., Zhang Y., et al. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22. J Hum Genet,2003,48(7):390-392.
[40]Liu P., Yang Q., Wang X., et al. Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3-q24.2. J Invest Dermatol,2007,
[41]Liu P., Yang Q., Wang X., et al. Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2. J Invest Dermatol,2008,128(6): 1418-1422.
[42]Smith F.J., Irvine A.D., Terron-Kwiatkowski A., et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet,2006,38(3): 337-342.
[43]Chen H., Ho J.C., Sandilands A., et al. Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris. J Invest Dermatol,2008,128(7):1669-1675.
[44]Nomura T A.M., Sandilands A, Nemoto-Hasebe I, Sakai K, Nagasaki A, Ota M, Hata H, Evans AT, Palmer CN, Shimizu H, McLean WH. Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan. J Invest Dermatol,2008,128(6.
[45]Nomura T S.A., Akiyama M, Liao H, Evans AT, Sakai K, Ota M, Sugiura H, Yamamoto K, Sato H, Palmer CN, Smith FJ, McLean WH, Shimizu H. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol,119(7.
[46]Gruber R., Janecke A.R., Fauth C., et al. Filaggrin mutations p.R501X and c.2282del4 in ichthyosis vulgaris. Eur J Hum Genet,2007,15(2):179-184.
[47]Sandilands A., O'Regan GM., Liao H., et al. Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis. J Invest Dermatol,2006,126(8):1770-1775.
[48]Sandilands A., Terron-Kwiatkowski A., Hull P.R., et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet,2007,39(5):650-654.
[49]Hamada T., Sandilands A., Fukuda S., et al. De novo occurrence of the filaggrin mutation p.R501X with prevalent mutation c.3321delA in a Japanese family with ichthyosis vulgaris complicated by atopic dermatitis. J Invest Dermatol,2008, 128(5):1323-1325.
[50]Moore MM R.-S.S., Rich-Edwards JW. Perinatal predictors of atopic dermatitis occurring in the pirst six months of life. Pediatrics,2004,113(7.
[51]Leung DY B.M., Howell MD. New insights into atopic dermatitis. J Clin Invest, 2004,113(8.
[52]Novak N., Bieber T.Leung D.Y. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol,2003,112(6 Suppl):S128-139.
[53]Cookson W.O.Moffatt M.F. The genetics of atopic dermatitis. Curr Opin Allergy Clin Immunol,2002,2(5):383-387.
[54]Cookson W.O., Ubhi B., Lawrence R., et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet,2001,27(4):372-373.
[55]Palmer C.N., Irvine A.D., Terron-Kwiatkowski A., et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet,2006,38(4):441-446.
[56]Barker JN P.C., Zhao Y, Liao H, Hull PR, Lee SP, Allen MH, Meggitt SJ, Reynolds NJ, Trembath RC, McLean WH. Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood. J Invest Dermatol,2007,127(7.
[57]Morar N., Cookson W.O., Harper J.I., et al. Filaggrin mutations in children with severe atopic dermatitis. J Invest Dermatol,2007,127(7):1667-1672.
[58]Weidinger S., Rodriguez E., Stahl C., et al. Filaggrin mutations strongly predispose to early-onset and extrinsic atopic dermatitis. J Invest Dermatol,2007, 127(3):724-726.
[59]Stemmler S., Parwez Q., Petrasch-Parwez E., et al. Two common loss-of-function mutations within the filaggrin gene predispose for early onset of atopic dermatitis. J Invest Dermatol,2007,127(3):722-724.
[60]Nemoto-Hasebe I., Akiyama M., Nomura T., et al. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema Br J Dermatol,2009,161(6):1387-1390.
[61]Lebwohl M. Psoriasis. Lancet,2003,361(8.
[62]刘刁骋.银屑病发病机制的研究进展.沈阳医学院学报,2007,9(1008-2344(2007)04-0248-03)：
[63]Bowcock A.M.Cookson W.O. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Hum Mol Genet,2004,13 Spec No l(R43-55.
[64]Farber E.M., Nall M.L.Watson W. Natural history of psoriasis in 61 twin pairs. Arch Dermatol,1974,109(2):207-211.
[65]Asumalahti K., Ameen M., Suomela S., et al. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol, 2003,120(4):627-632.
[66]Capon F H.C., Veal CD, Tillman D, Burden AD, Barker JN, Bowcock AM, Trembath RC. Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis. J Med Genet,2004, 41(6)(60.
[67]Matthews D F.L., Powles A, Weber J, McCarthy M, Fisher E, Davies K, Williamson R. Evidence that a locus for familial psoriasis maps to chromosome 4q. Nat Genet,1998,14(2)(3.
[68]Capon F., Novelli G, Semprini S., et al. Searching for psoriasis susceptibility genes in Italy:genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol,1999,112(1):32-35.
[69]Enlund F., Samuelsson L., Enerback C., et al. Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden. Eur J Hum Genet,1999,7(7):783-790.
[70]Lee Y.A., Ruschendorf F., Windemuth C., et al. Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13. Am J Hum Genet,2000,67(4):1020-1024.
[71]Parham C C.M., Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbetal and a novel cytokine receptor subunit, IL-23R J Immunol,2002, 168(11)(10.
[72]Nair R.P., Henseler T., Jenisch S., et al. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum Mol Genet,1997,6(8):1349-1356.
[73]Zhang XJ H.P., Wang ZX, Zhang J, Li YB, Wang HY, Wei SC, Chen SY, Xu SJ, Jin L, Yang S, Huang W. Evidence for a major psoriasis susceptibility locus at 6p21(PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese hans. J Invest Dermatol.,2002,119(6)(6.
[74]Asumalahti K., Laitinen, T., Lahermo, P., Suomela, S., Itkonen-Vatjus, R., Jansen, C., Karvonen, J., Karvonen, S.-L., Reunala, T., Snellman, E., Uurasmaa, T., Saarialho-Kere, U., Kere, J. Psoriasis susceptibility locus on 18p revealed by genome scan in Finnish families not associated with PSORS1. J. Invest. Derm, 2003,121(6.
[75]Cargill M., Schrodi, S. J., Chang, M., Garcia, V. E., Brandon, R., Callis, K. P., Matsunami, N., Ardlie, K. G, Civello, D., Catanese, J. J., Leong, D. U., Panko, J. M., McAllister, L. B., Hansen, C. B., Papenfuss, J., Prescott, S. M., White, T. J., Leppert, M. F., Krueger, G. G., Begovich, A. B. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet,2007,80(117.
[76]Capon F B.M., Wolf N, Quaranta M, Huffmeier U, Allen M, Timms K, Abkevich V, Gutin A, Smith R, Warren RB, Young HS, Worthington J, Burden AD, Griffiths CE, Hayday A, Nestle FO, Reis A, Lanchbury J, Barker JN, Trembath RC. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet,2008,17(13)(45):1938.
[77]Rebala K., Szczerkowska-Dobosz A., Niespodziana K., et al. Simple and rapid screening for HLA-Cw*06 in Polish patients with psoriasis. Clin Exp Dermatol, 2009,
[78]Zhang X.J. [Enlightenment from genome-wide association study to genetics of psoriasis]. Zhejiang Da Xue Xue Bao Yi Xue Ban,2009,38(4):333-337.
[79]Nair R.P., Duffin K.C., Helms C., et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet,2009,41(2):199-204.
[80]Huffmeier U B.J., Becker T, Armour JA, Traupe H, Estivill X, Riveira-Munoz E, Mossner R, Reich K, Kurrat W, Wienker TF, Schalkwijk J, Zeeuwen PL, Reis A.Institute of Human Genetics U.H.E., University Erlangen-Nuremberg, Erlangen, Germany. Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. J Invest Dermatol,2010,130(4)(6.
[81]Huffmeier U T.H., Oji V, Lascorz J, Stander M, Lohmann J, Wendler J, Burkhardt H, Reis A. Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients. J Invest Dermatol,2007,127(6)(1367-1370.
[82]Chang YC W.W., Chen CH, Hu CF, Hsu LA. Association between P478S polymorphism of the filaggrin gene and risk of psoriasis in a Chinese population in Taiwan. Arch Dermatol Res,2008,300(3)(7.
[83]McGrath J.A.Uitto J. The filaggrin story:novel insights into skin-barrier function and disease. Trends Mol Med,2008,14(1):20-27.
[84]Kezic S., Kammeyer A., Calkoen F., et al. Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods. Br J Dermatol,2009,161(5): 1098-1104.
[85]Sandilands A., Sutherland C., Irvine A.D., et al. Filaggrin in the frontline:role in skin barrier function and disease. J Cell Sci,2009,122(Pt 9):1285-1294.
[86]Fallon P.G., Sasaki T., Sandilands A., et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet,2009,41(5):602-608.
[2]Lebwohl M. Psoriasis. Lancet,2003,361(8.
[3]刘刁骋.银屑病发病机制的研究进展.沈阳医学院学报,2007,9(1008-2344(2007)04-0248-03)：
[4]Bouwstra J.A.Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta,2006,1758(12):2080-2095.
[5]Farber E.M., Nall M.L.Watson W. Natural history of psoriasis in 61 twin pairs. Arch Dermatol,1974,109(2):207-211.
[6]Brandrup F., Green A.Holm N. [Occurrence of psoriasis in Denmark]. Ugeskr Laeger,1982,144(47):3538-3541.
[7]Farber E.M.Nall M.L. The natural history of psoriasis in 5,600 patients. Dermatologica,1974,148(1):1-18.
[8]Asumalahti K., Ameen M., Suomela S., et al. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol, 2003,120(4):627-632.
[9]Capon F H.C., Veal CD, Tillman D, Burden AD, Barker JN, Bowcock AM, Trembath RC. Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis. J Med Genet,2004, 41(6)(60.
[10]Matthews D F.L., Powles A, Weber J, McCarthy M, Fisher E, Davies K, Williamson R. Evidence that a locus for familial psoriasis maps to chromosome 4q. Nat Genet,1998,14(2)(3.
[11]Capon F., Novelli G, Semprini S., et al. Searching for psoriasis susceptibility genes in Italy:genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol,1999,112(1):32-35.
[12]Enlund F., Samuelsson L., Enerback C., et al. Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden. Eur J Hum Genet,1999,7(7):783-790.
[13]Lee Y.A., Ruschendorf F., Windemuth C., et al. Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13. Am J Hum Genet,2000,67(4):1020-1024.
[14]Parham C C.M., Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbetal and a novel cytokine receptor subunit, IL-23R J Immunol,2002, 168(11)(10.
[15]Nair R.P., Henseler T., Jenisch S., et al. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan Hum Mol Genet,1997,6(8):1349-1356.
[16]Zhang XJ H.P., Wang ZX, Zhang J, Li YB, Wang HY, Wei SC, Chen SY, Xu SJ, Jin L, Yang S, Huang W. Evidence for a major psoriasis susceptibility locus at 6p21(PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese hans. J Invest Dermatol.,2002,119(6)(6.
[17]Asumalahti K., Laitinen, T., Lahermo, P., Suomela, S., Itkonen-Vatjus, R., Jansen, C., Karvonen, J., Karvonen, S.-L., Reunala, T., Snellman, E., Uurasmaa, T., Saarialho-Kere, U., Kere, J. Psoriasis susceptibility locus on 18p revealed by genome scan in Finnish families not associated with PSORS1. J. Invest. Derm, 2003,121(6.
[18]Cargill M., Schrodi, S. J., Chang, M., Garcia, V. E., Brandon, R., Callis, K. P., Matsunami, N., Ardlie, K. G, Civello, D., Catanese, J. J., Leong, D. U., Panko, J. M., McAllister, L. B., Hansen, C. B., Papenfuss, J., Prescott, S. M., White, T. J., Leppert, M. F., Krueger, G. G., Begovich, A. B. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet,2007,80(117.
[19]Capon F B.M., Wolf N, Quaranta M, Huffmeier U, Allen M, Timms K, Abkevich V, Gutin A, Smith R, Warren RB, Young HS, Worthington J, Burden AD, Griffiths CE, Hayday A, Nestle FO, Reis A, Lanchbury J, Barker JN, Trembath RC. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet,2008,17(13)(45):1938.
[20]Rebala K., Szczerkowska-Dobosz A., Niespodziana K., et al. Simple and rapid screening for HLA-Cw*06 in Polish patients with psoriasis. Clin Exp Dermatol, 2009,
[21]Zhang X.J. [Enlightenment from genome-wide association study to genetics of psoriasis]. Zhejiang Da Xue Xue Bao Yi Xue Ban,2009,38(4):333-337.
[22]Nair R.P., Duffin K.C., Helms C., et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet,2009,41(2):199-204.
[23]Huffmeier U B.J., Becker T, Armour JA, Traupe H, Estivill X, Riveira-Munoz E, Mossner R, Reich K, Kurrat W, Wienker TF, Schalkwijk J, Zeeuwen PL, Reis A.Institute of Human Genetics U.H.E., University Erlangen-Nuremberg, Erlangen, Germany. Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. J Invest Dermatol,2010,130(4)(6.
[24]Giardina E., Capon F., De Rosa M.C., et al. Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus. Ann Hum Genet,2004,68(Pt 6):639-645.
[25]Chen H., Toh T.K., Szeverenyi I., et al. Association of skin barrier genes within the PSORS4 locus is enriched in Singaporean Chinese with early-onset psoriasis. J Invest Dermatol,2009,129(3):606-614.
[26]Zhang XJ H.W., Yang S, Sun LD, Zhang FY, Zhu QX, Zhang FR, Zhang C, Du WH, Pu XM, Li H, Xiao FL, Wang ZX, Cui Y, Hao F, Zheng J, Yang XQ, Cheng H, He CD, Liu XM, Xu LM, Zheng HF, Zhang SM, Zhang JZ, Wang HY, Cheng YL, Ji BH, Fang QY, Li YZ, Zhou FS, Han JW, Quan C, Chen B, Liu JL, Lin D, Fan L, Zhang AP, Liu SX, Yang CJ, Wang PG, Zhou WM, Lin GS, Wu WD, Fan X, Gao M, Yang BQ, Lu WS, Zhang Z, Zhu KJ, Shen SK, Li M, Zhang XY, Cao TT, Ren W, Zhang X, He J, Tang XF, Lu S, Yang JQ, Zhang L, Wang DN, Yuan F, Yin XY, Huang HJ, Wang HF, Lin XY, Liu JJ. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet,2009,41(2):205-210.
[27]de Cid R R.-M.E., Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramis G, Ballana E, Martin-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I, Eichler EE, Lazaro C, Pujol RM, Armengol L, Abecasis G, Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet,2009,41(2):211-215.
[28]Hoffjan S.Stemmler S. On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. Br J Dermatol,2007,157(3): 441-449.
[29]de Guzman Strong C., Conlan S., Deming C.B., et al. A milieu of regulatory elements in the epidermal differentiation complex syntenic block:implications for atopic dermatitis and psoriasis. Hum Mol Genet,2010,19(8):1453-1460.
[30]Mischke D K.B., Marenholz I, Volz A, Ziegler A. Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. J Invest Dermatol,1996,106(5):989-992.
[31]Gan S.Q., McBride O.W., Idler W.W., et al. Organization, structure, and polymorphisms of the human profilaggrin gene. Biochemistry,1991,30(23): 5814.
[32]Markova NG M.L., Chipev CC, Gan SQ, Idler WW, Steinert PM. Profilaggrin is a major epidermal calcium-binding protein. Mol Cell Biol,1993,13(1)(613-625.
[33]Smith F.J., Irvine A.D., Terron-Kwiatkowski A., et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet,2006,38(3): 337-342.
[34]Presland R.B., Boggess D., Lewis S.P., et al. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice:an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol,2000,115(6):1072-1081.
[35]Huffmeier U T.H., Oji V, Lascorz J, Stander M, Lohmann J, Wendler J, Burkhardt H, Reis A. Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients. J Invest Dermatol,2007,127(6)(1367-1370.
[36]Chang YC W.W., Chen CH, Hu CF, Hsu LA. Association between P478S polymorphism of the filaggrin gene and risk of psoriasis in a Chinese population in Taiwan. Arch Dermatol Res,2008,300(3)(7.
[37]Sambrook J R.D. Molecular Cloning:A Laboratry Manual(分子克隆实验指南,黄培堂等译).2002,463-471.
[38]Sandilands A., Terron-Kwiatkowski A., Hull P.R., et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema Nat Genet,2007,39(5):650-654.
[39]Nomura T., Sandilands A., Akiyama M., et al. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol,2007,119(2):434-440.
[40]Nemoto-Hasebe I., Akiyama M., Nomura T., et al. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema Br J Dermatol,2009,161(6):1387-1390.
[41]Fallon P.G., Sasaki T., Sandilands A., et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet,2009,41(5):602-608.
[42]Scharschmidt T.C., Man M.Q., Hatano Y., et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol,2009,124(3):496-506,506 e491-496.
[43]Palmer C.N., Irvine A.D., Terron-Kwiatkowski A., et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet,2006,38(4):441-446.
[44]Liao H., Waters A.J., Goudie D.R., et al. Filaggrin Mutations Are Genetic Modifying Factors Exacerbating X-Linked Ichthyosis. J Invest Dermatol,2007,
[45]Walley A.J., Chavanas S., Moffatt M.F., et al. Gene polymorphism in Netherton and common atopic disease. Nat Genet,2001,29(2):175-178.
[46]Vasilopoulos Y., Cork M.J., Murphy R., et al. Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis. J Invest Dermatol,2004,123(1):62-66.
[47]Kanner L. Follow-up study of eleven autistic children originally reported in 1943. J Autism Child Schizophr,1971,1(2):119-145.
[48]Lainhart J.E., Ozonoff S., Coon H., et al. Autism, regression, and the broader autism phenotype. Am J Med Genet,2002,113(3):231-237.
[49]Sutcliffe J.S. Genetics. Insights into the pathogenesis of autism. Science,2008, 321(5886):208-209.
[50]Bailey A., Le Couteur A., Gottesman I., et al. Autism as a strongly genetic disorder:evidence from a British twin study. Psychol Med,1995,25(1):63-77.
[51]Szatmari P., Jones M.B., Zwaigenbaum L., et al. Genetics of autism:overview and new directions. J Autism Dev Disord,1998,28(5):351-368.
[52]Rutter M. Genetic studies of autism:from the 1970s into the millennium. J Abnorm Child Psychol,2000,28(1):3-14.
[53]Bartlett C.W., Goedken R.Vieland V.J. Effects of updating linkage evidence across subsets of data:reanalysis of the autism genetic resource exchange data set Am J Hum Genet,2005,76(4):688-695.
[54]Maussion G, Carayol J., Lepagnol-Bestel A.M., et al. Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism. Hum Mol Genet,2008,17(16):2541-2551.
[55]Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum Mol Genet,2001,10(9):973-982.
[56]Buxbaum J.D., Silverman J.M., Smith C.J., et al. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. Am J Hum Genet,2001,68(6):1514-1520.
[57]A genomewide screen for autism:strong evidence for linkage to chromosomes 2q,7q, and 16p. Am J Hum Genet,2001,69(3):570-581.
[58]Auranen M., Vanhala R., Varilo T., et al. A genomewide screen for autism-spectrum disorders:evidence for a major susceptibility locus on chromosome 3q25-27. Am J Hum Genet,2002,71(4):777-790.
[59]Yu C.E., Dawson G, Munson J., et al. Presence of large deletions in kindreds with autism. Am J Hum Genet,2002,71(1):100-115.
[60]Trikalinos T.A., Karvouni A., Zintzaras E., et al. A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol Psychiatry,2006,11(1): 29-36.
[61]A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium. Hum Mol Genet,1998,7(3):571-578.
[62]Alarcon M., Cantor R.M., Liu J., et al. Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families. Am J Hum Genet,2002, 70(1):60-71.
[63]Molloy C.A., Keddache M.Martin L.J. Evidence for linkage on 21q and 7q in a subset of autism characterized by developmental regression. Mol Psychiatry, 2005,10(8):741-746.
[64]Ma D.Q., Cuccaro M.L., Jaworski J.M., et al. Dissecting the locus heterogeneity of autism:significant linkage to chromosome 12q14. Mol Psychiatry,2007,12(4): 376-384.
[65]Ritvo E.R., Mason-Brothers A., Menkes J.H., et al. Association of autism, retinoblastoma, and reduced esterase D activity. Arch Gen Psychiatry,1988, 45(6):600.
[66]Bradford Y., Haines J., Hutcheson H., et al. Incorporating language phenotypes strengthens evidence of linkage to autism. Am J Med Genet,2001,105(6): 539-547.
[67]Clayton-Smith J., Webb T., Cheng X.J., et al. Duplication of chromosome 15 in the region 15q11-13 in a patient with developmental delay and ataxia with similarities to Angelman syndrome. J Med Genet,1993,30(6):529-531.
[68]Bundey S., Hardy C., Vickers S., et al. Duplication of the 15q11-13 region in a patient with autism, epilepsy and ataxia Dev Med Child Neurol,1994,36(8): 736-742.
[69]Hernando C., Plaja A., Rigola M.A., et al. Comparative genomic hybridisation shows a partial de novo deletion 16p11.2 in a neonate with multiple congenital malformations. J Med Genet,2002,39(5):E24.
[70]Shimojima K., Inoue T., Fujii Y., et al. A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and hemivertebrae. Eur J Med Genet, 2009,52(6):433-435.
[71]Yonan A.L., Alarcon M., Cheng R., et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet,2003,73(4):886-897.
[72]Stone J.L., Merriman B., Cantor R.M., et al. Evidence for sex-specific risk alleles in autism spectrum disorder. Am J Hum Genet,2004,75(6):1117-1123.
[73]Cantor R.M., Kono N., Duvall J.A., et al. Replication of autism linkage: fine-mapping peak at 17q21. Am J Hum Genet,2005,76(6):1050-1056.
[74]Thomas N.S., Sharp A.J., Browne C.E., et al. Xp deletions associated with autism in three females. Hum Genet,1999,104(1):43-48.
[75]Jamain S., Quach H., Betancur C., et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet, 2003,34(1):27-29.
[76]Lam C.W., Yeung W.L., Ko C.H., et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet,2000, 37(12):E41.
[77]Herault J., Petit E., Martineau J., et al. Autism and genetics:clinical approach and association study with two markers of HRAS gene. Am J Med Genet,1995, 60(4):276-281.
[78]Comings D.E., Wu S., Chiu C., et al. Studies of the c-Harvey-Ras gene in psychiatric disorders. Psychiatry Res,1996,63(1):25-32.
[79]Kim S J., Brune C.W., Kistner E.O., et al. Transmission disequilibrium testing of the chromosome 15q11-q13 region in autism. Am J Med Genet B Neuropsychiatr Genet,2008,147B(7):1116-1125.
[80]Jacob S., Landeros-Weisenberger A.Leckman J.F. Autism spectrum and obsessive-compulsive disorders:OC behaviors, phenotypes and genetics. Autism Res,2009,2(6):293-311.
[81]Cook E.H., Jr.Scherer S.W. Copy-number variations associated with neuropsychiatric conditions. Nature,2008,455(7215):919-923.
[82]Golimbet V.E.Koren E.V. [Copy number variations in the human genome-a new page in psychiatric genetics:the collaborative project PsychCNV's]. Zh Nevrol Psikhiatr Im S S Korsakova,2010,110(1):107-109.
[83]Sebat J., Lakshmi B., Malhotra D., et al. Strong association of de novo copy number mutations with autism. Science,2007,316(5823):445-449.
[84]Kusenda M. Sebat J. The role of rare structural variants in the genetics of autism spectrum disorders. Cytogenet Genome Res,2008,123(1-4):36-43.
[85]Zhao X., Pak C., Smrt R.D., et al. Epigenetics and Neural developmental disorders:Washington DC, September 18 and 19,2006. Epigenetics,2007,2(2): 126-134.
[86]Gonzales M.L.LaSalle J.M. The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep,2010,12(2):127-134.
[87]Currenti S.A. Understanding and determining the etiology of autism. Cell Mol Neurobiol,2010,30(2):161-171.
[88]Scheiffele P., Fan J., Choih J., et al. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell,2000,101(6): 657-669.
[89]Ichtchenko K., Nguyen T.Sudhof T.C. Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem,1996,271(5):2676-2682.
[90]Ichtchenko K., Hata Y., Nguyen T., et al. Neuroligin 1:a splice site-specific ligand for beta-neurexins. Cell,1995,81(3):435-443.
[91]Laumonnier F., Bonnet-Brilhault F., Gomot M., et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet,2004,74(3):552-557.
[92]Ylisaukko-oja T., Alarcon M., Cantor R.M., et al. Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families. Ann Neurol,2006,59(1):145-155.
[93]Blasi F., Bacchelli E., Pesaresi G, et al. Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am J Med Genet B Neuropsychiatr Genet,2006,141B(3): 220-221.
[94]Talebizadeh Z., Bittel D.C., Veatch O.J., et al. Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism? J Autism Dev Disord,2004,34(6): 735-736.
[95]Yan J., Feng J., Schroer R., et al. Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr Genet,2008,18(4):204-207.
[96]Koehnke J., Jin X., Budreck E.C., et al. Crystal structure of the extracellular cholinesterase-like domain from neuroligin-2. Proc Natl Acad Sci USA,2008, 105(6):1873-1878.
[97]Rao A., Harms K.J.Craig A.M. Neuroligation:building synapses around the neurexin-neuroligin link. Nat Neurosci,2000,3(8):747-749.
[98]Dean C., Scholl F.G., Choih J., et al. Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci,2003,6(7):708-716.
[99]Tabuchi K., Blundell J., Etherton M.R., et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science,2007, 318(5847):71-76.
[100]Jamain S., Radyushkin K., Hammerschmidt K., et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci USA,2008,105(5):1710-1715.
[1]McGrath JA U.J. The filaggrin story:novel insights into skin-barrier function and disease. Trends Mol Med,2008,14(1)(20-27.
[2]Bouwstra J.A.Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta,2006,1758(12):2080-2095.
[3]Volz A., Korge B.P., Compton J.G., et al. Physical mapping of a functional cluster of epidermal differentiation genes on chromosome 1q21. Genomics,1993, 18(1):92-99.
[4]Shwayder T.Akland T. Neonatal skin barrier:structure, function, and disorders. Dermatol Ther,2005,18(2):87-103.
[5]McKinley-Grant L.J., Idler W.W., Bernstein I.A., et al. Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21. Proc Natl Acad Sci USA,1989,86(13):4848-4852.
[6]Presland R.B., Haydock P.V., Fleckman P., et al. Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. J Biol Chem,1992, 267(33):23772-23781.
[7]Gan S.Q., McBride O.W., Idler W.W., et al. Organization, structure, and polymorphisms of the human profilaggrin gene. Biochemistry,1991,30(23): 5814.
[8]Markova NG M.L., Chipev CC, Gan SQ, Idler WW, Steinert PM. Profilaggrin is a major epidermal calcium-binding protein Mol Cell Biol,1993,13(1)(613-625.
[9]Jang SI S.P., Markova NG. Activator protein 1 activity is involved in the regulation of the cell type-specific expression from the proximal promoter of the human profilaggrin gene. J Biol Chem,1996,271(39)(24105-24114.
[10]Jang SI K.-J.N., Morasso MI, Steinert PM, Markova NG. Complex interactions between epidermal POU domain and activator protein 1 transcription factors regulate the expression of the profilaggrin gene in normal human epidermal keratinocytes. J Biol Chem,2000,275(20)(15295-15304.
[11]King KE P.R., Gerdes MJ, Tokino T, Yamashita T, Baker CC, Weinberg WC. Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis. Carcinogenesis,2006,27(1)(53-63.
[12]Candi E R.A., Terrinoni A, Giamboi-Miraglia A, Lena AM, Mantovani R, Knight R, Melino G. DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci U S A,2007, 104(29)(11999-12004.
[13]Park GT M.M. Regulation of the Dlx3 homeobox gene upon differentiation of mouse keratinocytes. J Biol Chem,1999,274(37)(26599-26608.
[14]Icre G, Wahli W.Michalik L. Functions of the peroxisome proliferator-activated receptor (PPAR) alpha and beta in skin homeostasis, epithelial repair, and morphogenesis. J Investig Dermatol Symp Proc,2006,11(1):30-35.
[15]Mao-Qiang M., Fowler A.J., Schmuth M., et al. Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation. J Invest Dermatol,2004,123(2):305-312.
[16]Presland R.B., Tomic-Canic M., Lewis S.P., et al. Regulation of human profilaggrin promoter activity in cultured epithelial cells by retinoic acid and glucocorticoids. J Dermatol Sci,2001,27(3):192-205.
[17]Presland R.B., Bassuk J.A., Kimball J.R., et al. Characterization of two distinct calcium-binding sites in the amino-terminus of human profilaggrin. J Invest Dermatol,1995,104(2):218-223.
[18]Laster A.J.Haynes B.F. Characterization of a monoclonal antibody, RTE-21, that binds to keratohyalin granule-associated proteins in epithelial cells of human skin and thymus. Clin Immunol Immunopathol,1986,41(1):130-144.
[19]Presland R.B., Kimball J.R., Kautsky M.B., et al. Evidence for specific proteolytic cleavage of the N-terminal domain of human profilaggrin during epidermal differentiation. J Invest Dermatol,1997,108(2):170-178.
[20]Kam E R.K., Lim SK, Dale BA. Identification of rat epidermal profilaggrin phosphatase as a member of the protein phosphatase 2A family. J Cell Sci,1993, 106(8.
[21]Tarcsa E., Marekov L.N., Mei G., et al. Protein unfolding by peptidylarginine deiminase. Substrate specificity and structural relationships of the natural substrates trichohyalin and filaggrin. J Biol Chem,1996,271(48):30709-30716.
[22]Mechin MC E.M., Nachat R, Chavanas S, Charveron M, Ishida-Yamamoto A, Serre G, Takahara H, Simon M. The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations. Cell Mol Life Sci,2005,62(17)(12.
[23]Denecker G, Hoste E., Gilbert B., et al. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat Cell Biol,2007,9(6):666-674.
[24]Denecker G, Ovaere P., Vandenabeele P., et al. Caspase-14 reveals its secrets. J Cell Biol,2008,180(3):451-458.
[25]Kamata Y., Taniguchi A., Yamamoto M., et al. Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids. J Biol Chem,2009,284(19):12829-12836.
[26]Rawlings A.V.Harding C.R. Moisturization and skin barrier function. Dermatol Ther,2004,17 Suppl 1(43-48.
[27]Presland R.B., Boggess D., Lewis S.P., et al. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice:an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol,2000,115(6):1072-1081.
[28]Schwartz D.R., Homanics G.E., Hoyt D.G., et al. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci USA,1999,96(8):4680-4685.
[29]Suchi M., Harada N., Wada Y, et al. Molecular cloning of a cDNA encoding human histidase. Biochim Biophys Acta,1993,1216(2):293-295.
[30]CR S.I.H. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol,1986,115(84-92.
[31]Katagiri C S., J., Nomura, J. and Denda, M. Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice. J. Dermatol Sci,2003,31(29-35.
[32]Wells R.S., Kerr CB. Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. Br Med J,1966,1(947-950.
[33]Lei G, Zhang YY H. Investigation on the prevalence of Ichthyosis in Sichuan province. Chin J Dermatol (in Chinese),1992,25(105-106.
[34]雷光鲁张.,胡应.四川省鱼鳞病流行病学调查报告.中华皮肤科杂志,1992,25(105-106.
[35]Sybert V.P., Dale B.A.Holbrook K.A. Ichthyosis vulgaris:identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. J Invest Dermatol,1985,84(3):191-194.
[36]Nirunsuksiri W P.R., Brumbaugh SG, Dale BA, Fleckman P. Decreased profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control. J Biol Chem,1995,270(6.
[37]Nirunsuksiri W., Zhang S.H.Fleckman P. Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with ichthyosis vulgaris. J Invest Dermatol,1998,110(6):854-861.
[38]Compton J.G., DiGiovanna J.J., Johnston K.A., et al. Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1. Exp Dermatol,2002,11(6):518-526.
[39]Zhong W., Cui B., Zhang Y., et al. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22. J Hum Genet,2003,48(7):390-392.
[40]Liu P., Yang Q., Wang X., et al. Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3-q24.2. J Invest Dermatol,2007,
[41]Liu P., Yang Q., Wang X., et al. Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2. J Invest Dermatol,2008,128(6): 1418-1422.
[42]Smith F.J., Irvine A.D., Terron-Kwiatkowski A., et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet,2006,38(3): 337-342.
[43]Chen H., Ho J.C., Sandilands A., et al. Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris. J Invest Dermatol,2008,128(7):1669-1675.
[44]Nomura T A.M., Sandilands A, Nemoto-Hasebe I, Sakai K, Nagasaki A, Ota M, Hata H, Evans AT, Palmer CN, Shimizu H, McLean WH. Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan. J Invest Dermatol,2008,128(6.
[45]Nomura T S.A., Akiyama M, Liao H, Evans AT, Sakai K, Ota M, Sugiura H, Yamamoto K, Sato H, Palmer CN, Smith FJ, McLean WH, Shimizu H. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol,119(7.
[46]Gruber R., Janecke A.R., Fauth C., et al. Filaggrin mutations p.R501X and c.2282del4 in ichthyosis vulgaris. Eur J Hum Genet,2007,15(2):179-184.
[47]Sandilands A., O'Regan GM., Liao H., et al. Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis. J Invest Dermatol,2006,126(8):1770-1775.
[48]Sandilands A., Terron-Kwiatkowski A., Hull P.R., et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet,2007,39(5):650-654.
[49]Hamada T., Sandilands A., Fukuda S., et al. De novo occurrence of the filaggrin mutation p.R501X with prevalent mutation c.3321delA in a Japanese family with ichthyosis vulgaris complicated by atopic dermatitis. J Invest Dermatol,2008, 128(5):1323-1325.
[50]Moore MM R.-S.S., Rich-Edwards JW. Perinatal predictors of atopic dermatitis occurring in the pirst six months of life. Pediatrics,2004,113(7.
[51]Leung DY B.M., Howell MD. New insights into atopic dermatitis. J Clin Invest, 2004,113(8.
[52]Novak N., Bieber T.Leung D.Y. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol,2003,112(6 Suppl):S128-139.
[53]Cookson W.O.Moffatt M.F. The genetics of atopic dermatitis. Curr Opin Allergy Clin Immunol,2002,2(5):383-387.
[54]Cookson W.O., Ubhi B., Lawrence R., et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet,2001,27(4):372-373.
[55]Palmer C.N., Irvine A.D., Terron-Kwiatkowski A., et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet,2006,38(4):441-446.
[56]Barker JN P.C., Zhao Y, Liao H, Hull PR, Lee SP, Allen MH, Meggitt SJ, Reynolds NJ, Trembath RC, McLean WH. Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood. J Invest Dermatol,2007,127(7.
[57]Morar N., Cookson W.O., Harper J.I., et al. Filaggrin mutations in children with severe atopic dermatitis. J Invest Dermatol,2007,127(7):1667-1672.
[58]Weidinger S., Rodriguez E., Stahl C., et al. Filaggrin mutations strongly predispose to early-onset and extrinsic atopic dermatitis. J Invest Dermatol,2007, 127(3):724-726.
[59]Stemmler S., Parwez Q., Petrasch-Parwez E., et al. Two common loss-of-function mutations within the filaggrin gene predispose for early onset of atopic dermatitis. J Invest Dermatol,2007,127(3):722-724.
[60]Nemoto-Hasebe I., Akiyama M., Nomura T., et al. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema Br J Dermatol,2009,161(6):1387-1390.
[61]Lebwohl M. Psoriasis. Lancet,2003,361(8.
[62]刘刁骋.银屑病发病机制的研究进展.沈阳医学院学报,2007,9(1008-2344(2007)04-0248-03)：
[63]Bowcock A.M.Cookson W.O. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Hum Mol Genet,2004,13 Spec No l(R43-55.
[64]Farber E.M., Nall M.L.Watson W. Natural history of psoriasis in 61 twin pairs. Arch Dermatol,1974,109(2):207-211.
[65]Asumalahti K., Ameen M., Suomela S., et al. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol, 2003,120(4):627-632.
[66]Capon F H.C., Veal CD, Tillman D, Burden AD, Barker JN, Bowcock AM, Trembath RC. Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis. J Med Genet,2004, 41(6)(60.
[67]Matthews D F.L., Powles A, Weber J, McCarthy M, Fisher E, Davies K, Williamson R. Evidence that a locus for familial psoriasis maps to chromosome 4q. Nat Genet,1998,14(2)(3.
[68]Capon F., Novelli G, Semprini S., et al. Searching for psoriasis susceptibility genes in Italy:genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol,1999,112(1):32-35.
[69]Enlund F., Samuelsson L., Enerback C., et al. Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden. Eur J Hum Genet,1999,7(7):783-790.
[70]Lee Y.A., Ruschendorf F., Windemuth C., et al. Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13. Am J Hum Genet,2000,67(4):1020-1024.
[71]Parham C C.M., Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbetal and a novel cytokine receptor subunit, IL-23R J Immunol,2002, 168(11)(10.
[72]Nair R.P., Henseler T., Jenisch S., et al. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum Mol Genet,1997,6(8):1349-1356.
[73]Zhang XJ H.P., Wang ZX, Zhang J, Li YB, Wang HY, Wei SC, Chen SY, Xu SJ, Jin L, Yang S, Huang W. Evidence for a major psoriasis susceptibility locus at 6p21(PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese hans. J Invest Dermatol.,2002,119(6)(6.
[74]Asumalahti K., Laitinen, T., Lahermo, P., Suomela, S., Itkonen-Vatjus, R., Jansen, C., Karvonen, J., Karvonen, S.-L., Reunala, T., Snellman, E., Uurasmaa, T., Saarialho-Kere, U., Kere, J. Psoriasis susceptibility locus on 18p revealed by genome scan in Finnish families not associated with PSORS1. J. Invest. Derm, 2003,121(6.
[75]Cargill M., Schrodi, S. J., Chang, M., Garcia, V. E., Brandon, R., Callis, K. P., Matsunami, N., Ardlie, K. G, Civello, D., Catanese, J. J., Leong, D. U., Panko, J. M., McAllister, L. B., Hansen, C. B., Papenfuss, J., Prescott, S. M., White, T. J., Leppert, M. F., Krueger, G. G., Begovich, A. B. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet,2007,80(117.
[76]Capon F B.M., Wolf N, Quaranta M, Huffmeier U, Allen M, Timms K, Abkevich V, Gutin A, Smith R, Warren RB, Young HS, Worthington J, Burden AD, Griffiths CE, Hayday A, Nestle FO, Reis A, Lanchbury J, Barker JN, Trembath RC. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet,2008,17(13)(45):1938.
[77]Rebala K., Szczerkowska-Dobosz A., Niespodziana K., et al. Simple and rapid screening for HLA-Cw*06 in Polish patients with psoriasis. Clin Exp Dermatol, 2009,
[78]Zhang X.J. [Enlightenment from genome-wide association study to genetics of psoriasis]. Zhejiang Da Xue Xue Bao Yi Xue Ban,2009,38(4):333-337.
[79]Nair R.P., Duffin K.C., Helms C., et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet,2009,41(2):199-204.
[80]Huffmeier U B.J., Becker T, Armour JA, Traupe H, Estivill X, Riveira-Munoz E, Mossner R, Reich K, Kurrat W, Wienker TF, Schalkwijk J, Zeeuwen PL, Reis A.Institute of Human Genetics U.H.E., University Erlangen-Nuremberg, Erlangen, Germany. Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. J Invest Dermatol,2010,130(4)(6.
[81]Huffmeier U T.H., Oji V, Lascorz J, Stander M, Lohmann J, Wendler J, Burkhardt H, Reis A. Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients. J Invest Dermatol,2007,127(6)(1367-1370.
[82]Chang YC W.W., Chen CH, Hu CF, Hsu LA. Association between P478S polymorphism of the filaggrin gene and risk of psoriasis in a Chinese population in Taiwan. Arch Dermatol Res,2008,300(3)(7.
[83]McGrath J.A.Uitto J. The filaggrin story:novel insights into skin-barrier function and disease. Trends Mol Med,2008,14(1):20-27.
[84]Kezic S., Kammeyer A., Calkoen F., et al. Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods. Br J Dermatol,2009,161(5): 1098-1104.
[85]Sandilands A., Sutherland C., Irvine A.D., et al. Filaggrin in the frontline:role in skin barrier function and disease. J Cell Sci,2009,122(Pt 9):1285-1294.
[86]Fallon P.G., Sasaki T., Sandilands A., et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet,2009,41(5):602-608.