类脂蛋白沉积症一家系基因突变的研究
摘要
目的：研究类脂蛋白沉积症一家系细胞外基质蛋白1(ECM1)的基因突变。方法：采用PCR扩增目的基因,DNA双向测序法直接检测类脂蛋白沉积症一家系的ECM1基因,并用DNA克隆测序法进行验证。结果：先证者、其弟弟和母亲均为杂合子,在1474位插入了一个碱基T,形成了移码突变,使终止密码子提前出现,父亲正常。在50个正常汉族人的ECM1基因上未发现此改变。结论：本家系类脂蛋白沉积症存在新的突变位点,其遗传方式不符合经典的常染色体隐性遗传。
Mutation analysis of the ECM1 gene in a Chinese family with lipoid proteinosis
Objective:A Chinese family with lipoid proteinosis is reported and extracellular matrix protein 1 (ECM1) was identified.
Methods:Polymerase chain reaction (PCR),DNA direct nucleotide squencing and Clone squencing were used in mutation analysis.
Results:Affected siblings and his mother were revealed to have a heterozygosis frameshift mutation,1473insT, in exon 10, which led to a premature stop codon downstream, which was not detected in 50 unrelated healthy controls.
Conclusion:The frameshift mutation is the underlying cause of lipoid proteinosis in this family, which is not due to common polymorphism.
Mutation analysis of the ECM1 gene in a Chinese family with lipoid proteinosis
Objective:A Chinese family with lipoid proteinosis is reported and extracellular matrix protein 1 (ECM1) was identified.
Methods:Polymerase chain reaction (PCR),DNA direct nucleotide squencing and Clone squencing were used in mutation analysis.
Results:Affected siblings and his mother were revealed to have a heterozygosis frameshift mutation,1473insT, in exon 10, which led to a premature stop codon downstream, which was not detected in 50 unrelated healthy controls.
Conclusion:The frameshift mutation is the underlying cause of lipoid proteinosis in this family, which is not due to common polymorphism.
引文
[1]Urbach E, Wiethe C. Lipoidosis cutis et mucosae. Virchows Arch A Pathol Pathol Anat,1929,273:285-319.
[2]Hamada T, McLean WHI, Ramsay M, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in theextracellular matrix protein 1 gene (ECM1). Hum Mol Genet,2002,11(7):833-840.
[3]Han B, Zhang X, Liu Q,et al. Homozygous missense mutation in the ECM1 gene in Chinese siblings with lipoid proteinosis. Acta Derm Venereol,2007,87(5):387-389.
[4]Wang CY, Zhang PZ, Zhang FR, etal. New compound heterozygous mutations in a Chinese family with lipoid proteinosis. Br J Dermatol,2006,155(2):470-472.
[1]Smits P, Ni J, Feng P et al. The human extracellular matrix gene 1(ECM1): genomic structure, cDNA cloning, expression pattern and chromosomal localization. Genomics,1997,45(3):487-495.
[2]Sercu S, Zhang M, Oyama N. Interaction of extracellular matrix protein 1 with extracellular matrix components:ECM1 is a basement membrane protein of the skin. J Invest Dermatol,2008,128(6):1397-1408.
[3]Uchida T, Hayashi H, Inaoki M. A failure of mucocutaneous lymphangiogenesis may underlie the clinical features of lipoid proteinosis. Br J Dermatol,2007,156(1):152-157.
[4]Chan I, Liu L, Hamada T, Sethuraman G, The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol,2007,16(11):881-890.
[5]Nasir M, Latif A, Ajmal M,et al. A novel homozygous 62-bp insertion in ECM1 causes lipoid proteinosis in a multigeneration Pakistani family. Br J Dermatol,2009,161 (3):688-690.
[6]Horev L, Wollina DU, Potikha T. Lipoid proteinosis:identification of two novel mutations in the human ECM-1 gene and lack of genotype-phenotype correlation. Acta Derm Venereol,2009,89(5):528-529.
[1]Urbach E, Wiethe C. Lipoidosis cutis et mucosae. Virchows Arch A Pathol Pathol Anat,1929,273:285-319.
[2]Hamada T, McLean WHI, Ramsay M, et al. Lipoid proteinosis maps to Iq21 and is caused by mutations in theextracellular matrix protein 1 gene (ECM1). Hum Mol Genet,2002,11(7):833-840.
[3]Sellami D, Masmoudi A, Turki H et al. Ophthalmic manifestations of lipoid proteinosis. Presse Med,2006,35(5part1):796-798.
[4]Pariak A H, Koybasi S, Boran C, et al. Lipoid proteinosis:an unusual presentation with verruca vulgaris. J Dermatol,2005,32(9):751-755.
[5]Hu S, Kuo TT, Hong HS. Lipoid proteinosis:report of a possible localized form on both hands and wrists. Int J Dermatol,2005,44(5):408-410.
[6]HamadaT.Lipoid proteinosis. Clin Exp Dermatol,2002,27(8):624-629.
[7]Teive HA, Pereira ER, Zavala JA, et al. Generalized dystonia and striatal calcifications with lipoid proteinosis. Neurology,2004,63(11):2168-2169.
[8]Wiest G, Lehner-Baumgartner E, Baumgartner C. Panic attacks in an individual with bilateral selective lesions of the amygdala. Arch Neurol,2006,63(12): 1798-1801.
[9]Siebert M, Markowitsch HJ, Bartel P. Amygdala, affect and cognition:evidence from 10 patients with Urbach-Wiethe disease. Brain,2003,126(Pt 12):2627-2637.
[10]Hamada T. Lipoid proteinosis. Clin Exp Dermatol,2002,27(8):624-629.
[11]Kowalewski C, Kozlowska A, Chan I, et al. Three-dimensional imaging reveals major changes in skin microvasculature in lipoid proteinosis and lichen sclerosus J Dermatol Sci,2005,38(3):215-224.
[12]Bauer EA, Santa-Cruz DJ, Eisen AZ. Lipoid proteinosis:in vivo and in vitro evidence for a lysosomal storage disease. J Invest Dermatol,1981,76(2):119-125.
[13]Olsen DR, Chu ML, Uitto J. Expression of basement membrane zone genes coding for type IV procollagen and laminin by human skin fibroblasts in vitro: elevated alpha 1 (IV) collagen mRNA levels in lipoid proteinosis. J Invest Dermatol,1988,90(5):734-738.
[14]Wong CK, Lin CS. Remarkable response of lipoid proteinosis to oral dimethyl sulphoxide. Br J Dermatol,1988,119(4):541-544.
[15]Ozkaya-Bayazit E, Ozarmagan G, Baykal C, Ulug T. [Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]. Hautarzt,1997,48(7):477-481.
[16]Akoglu G, Karaduman A, Ergin S,et al. Clinical and histopathological response to acitretin therapy in lipoid proteinosis.J Dermatolog Treat.2010,[Epub ahead of print].
[17]Toosi S, Ehsani AH. Treatment of lipoid proteinosis with acitretin:a case report. J Eur Acad Dermatol Venereol,2009,23(4):482-483.
[18]Kaya T I, Kokturk A, Tursen U, et al. D-penicillamine treatment for lipoid proteinosis. Pediatr Dermatol,2002,19(4):359-362.
[19]Smits P, Ni J, Feng P et al. The human extracellular matrix gene 1(ECM1): genomic structure, cDNA cloning, expression pattern and chromosomal localization. Genomics,1997,45(3):487-495.
[20]Horev L, Potikha T, Ayalon S,et al. A novel splice-site mutation in ECM-1 gene in a consanguineous family with lipoid proteinosis. Exp Dermatol,2005,14(12):891-897.
[21]Mathieu E, Meheus L, Raymackers J, et al. Characterization of the osteogenic stromal cell line MN7:identification of secreted MN7 proteins using two-dimensional polyacrylamide gel electrophoresis, western blotting, and microsequencing. J Bone Miner Res,1994,9(6):903-913.
[22]Smits P, Poumay Y, Karperien M, et al. Differentiation-dependent alternative splicing and expression of the extracellular matrix protein 1 gene in human keratinocytes.J Invest Dermatol,2000,114(4):718-724.
[23]Horev L, Potikha T, Ayalon S, et al.A novel splice-site mutation in ECM-1 gene in a consanguineous family with lipoid proteinosis. Exp Dermatol,2005,14(12):891-789.
[24]Chan I, El-Zurghany A, Zendah B, et al. Molecular basis of lipoid proteinosis in a Libyan family. Clin Exp Dermatol,2003,28(5):545-548.
[25]Hamada T, Wessagowit V, South AP, et al. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation.J Invest Dermatol,2003,120(3):345-530.
[26]Desmet S, Devos SA, Chan I, et al. Clinical and molecular abnormalities in lipoid proteinosis. Eur J Dermatol,2005,15(5):344-346.
[27]Uchida T, Hayashi H, Inaoki M, etal. A failure of mucocutaneous lymphangiogenesis may underlie the clinical features of lipoid proteinosis. Br J Dermatol,2007,156(1):152-157.
[28]Chan I, Bingewar G, Patil K, et al. An Indian child with lipoid proteinosis resulting from a recurrent frameshift mutation (507delT) in the extracellular matrix protein 1 gene. Br J Dermatol,2004,151(3):726-727.
[29]Lupo I, Cefalu AB, Bongiorno MR, etal. A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily. Br J Dermatol,2005,153(5):1019-1022.
[30]Di Giandomenico S, Masi R, Cassandrini D,et al. Lipoid proteinosis:case report and review of the literature. Acta Otorhinolaryngol Ital,2006,26(3):162-167.
[31]Han B, Zhang X, Liu Q,et al. Homozygous missense mutation in the ECM1 gene in Chinese siblings with lipoid proteinosis. Acta Derm Venereol,2007,87(5):387-389.
[32]Wang CY, Zhang PZ, Zhang FR, etal. New compound heterozygous mutations in a Chinese family with lipoid proteinosis. Br J Dermatol,2006,155(2):470-472.
[33]Chan I, Sethuraman G, Sharma VK, et al. Molecular basis of lipoid proteinosis in two Indian siblings.J Dermatol,2004,31(9):764-766.
[34]Nasir M, Latif A, Ajmal M,et al. A novel homozygous 62-bp insertion in ECM1 causes lipoid proteinosis in a multigeneration Pakistani family. Br J Dermatol,2009,161(3):688-690.
[35]Horev L, Wollina DU, Potikha T. Lipoid proteinosis:identification of two novel mutations in the human ECM-1 gene and lack of genotype-phenotype correlation.Acta Derm Venereol,2009,89(5):528-529.
[2]Hamada T, McLean WHI, Ramsay M, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in theextracellular matrix protein 1 gene (ECM1). Hum Mol Genet,2002,11(7):833-840.
[3]Han B, Zhang X, Liu Q,et al. Homozygous missense mutation in the ECM1 gene in Chinese siblings with lipoid proteinosis. Acta Derm Venereol,2007,87(5):387-389.
[4]Wang CY, Zhang PZ, Zhang FR, etal. New compound heterozygous mutations in a Chinese family with lipoid proteinosis. Br J Dermatol,2006,155(2):470-472.
[1]Smits P, Ni J, Feng P et al. The human extracellular matrix gene 1(ECM1): genomic structure, cDNA cloning, expression pattern and chromosomal localization. Genomics,1997,45(3):487-495.
[2]Sercu S, Zhang M, Oyama N. Interaction of extracellular matrix protein 1 with extracellular matrix components:ECM1 is a basement membrane protein of the skin. J Invest Dermatol,2008,128(6):1397-1408.
[3]Uchida T, Hayashi H, Inaoki M. A failure of mucocutaneous lymphangiogenesis may underlie the clinical features of lipoid proteinosis. Br J Dermatol,2007,156(1):152-157.
[4]Chan I, Liu L, Hamada T, Sethuraman G, The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol,2007,16(11):881-890.
[5]Nasir M, Latif A, Ajmal M,et al. A novel homozygous 62-bp insertion in ECM1 causes lipoid proteinosis in a multigeneration Pakistani family. Br J Dermatol,2009,161 (3):688-690.
[6]Horev L, Wollina DU, Potikha T. Lipoid proteinosis:identification of two novel mutations in the human ECM-1 gene and lack of genotype-phenotype correlation. Acta Derm Venereol,2009,89(5):528-529.
[1]Urbach E, Wiethe C. Lipoidosis cutis et mucosae. Virchows Arch A Pathol Pathol Anat,1929,273:285-319.
[2]Hamada T, McLean WHI, Ramsay M, et al. Lipoid proteinosis maps to Iq21 and is caused by mutations in theextracellular matrix protein 1 gene (ECM1). Hum Mol Genet,2002,11(7):833-840.
[3]Sellami D, Masmoudi A, Turki H et al. Ophthalmic manifestations of lipoid proteinosis. Presse Med,2006,35(5part1):796-798.
[4]Pariak A H, Koybasi S, Boran C, et al. Lipoid proteinosis:an unusual presentation with verruca vulgaris. J Dermatol,2005,32(9):751-755.
[5]Hu S, Kuo TT, Hong HS. Lipoid proteinosis:report of a possible localized form on both hands and wrists. Int J Dermatol,2005,44(5):408-410.
[6]HamadaT.Lipoid proteinosis. Clin Exp Dermatol,2002,27(8):624-629.
[7]Teive HA, Pereira ER, Zavala JA, et al. Generalized dystonia and striatal calcifications with lipoid proteinosis. Neurology,2004,63(11):2168-2169.
[8]Wiest G, Lehner-Baumgartner E, Baumgartner C. Panic attacks in an individual with bilateral selective lesions of the amygdala. Arch Neurol,2006,63(12): 1798-1801.
[9]Siebert M, Markowitsch HJ, Bartel P. Amygdala, affect and cognition:evidence from 10 patients with Urbach-Wiethe disease. Brain,2003,126(Pt 12):2627-2637.
[10]Hamada T. Lipoid proteinosis. Clin Exp Dermatol,2002,27(8):624-629.
[11]Kowalewski C, Kozlowska A, Chan I, et al. Three-dimensional imaging reveals major changes in skin microvasculature in lipoid proteinosis and lichen sclerosus J Dermatol Sci,2005,38(3):215-224.
[12]Bauer EA, Santa-Cruz DJ, Eisen AZ. Lipoid proteinosis:in vivo and in vitro evidence for a lysosomal storage disease. J Invest Dermatol,1981,76(2):119-125.
[13]Olsen DR, Chu ML, Uitto J. Expression of basement membrane zone genes coding for type IV procollagen and laminin by human skin fibroblasts in vitro: elevated alpha 1 (IV) collagen mRNA levels in lipoid proteinosis. J Invest Dermatol,1988,90(5):734-738.
[14]Wong CK, Lin CS. Remarkable response of lipoid proteinosis to oral dimethyl sulphoxide. Br J Dermatol,1988,119(4):541-544.
[15]Ozkaya-Bayazit E, Ozarmagan G, Baykal C, Ulug T. [Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]. Hautarzt,1997,48(7):477-481.
[16]Akoglu G, Karaduman A, Ergin S,et al. Clinical and histopathological response to acitretin therapy in lipoid proteinosis.J Dermatolog Treat.2010,[Epub ahead of print].
[17]Toosi S, Ehsani AH. Treatment of lipoid proteinosis with acitretin:a case report. J Eur Acad Dermatol Venereol,2009,23(4):482-483.
[18]Kaya T I, Kokturk A, Tursen U, et al. D-penicillamine treatment for lipoid proteinosis. Pediatr Dermatol,2002,19(4):359-362.
[19]Smits P, Ni J, Feng P et al. The human extracellular matrix gene 1(ECM1): genomic structure, cDNA cloning, expression pattern and chromosomal localization. Genomics,1997,45(3):487-495.
[20]Horev L, Potikha T, Ayalon S,et al. A novel splice-site mutation in ECM-1 gene in a consanguineous family with lipoid proteinosis. Exp Dermatol,2005,14(12):891-897.
[21]Mathieu E, Meheus L, Raymackers J, et al. Characterization of the osteogenic stromal cell line MN7:identification of secreted MN7 proteins using two-dimensional polyacrylamide gel electrophoresis, western blotting, and microsequencing. J Bone Miner Res,1994,9(6):903-913.
[22]Smits P, Poumay Y, Karperien M, et al. Differentiation-dependent alternative splicing and expression of the extracellular matrix protein 1 gene in human keratinocytes.J Invest Dermatol,2000,114(4):718-724.
[23]Horev L, Potikha T, Ayalon S, et al.A novel splice-site mutation in ECM-1 gene in a consanguineous family with lipoid proteinosis. Exp Dermatol,2005,14(12):891-789.
[24]Chan I, El-Zurghany A, Zendah B, et al. Molecular basis of lipoid proteinosis in a Libyan family. Clin Exp Dermatol,2003,28(5):545-548.
[25]Hamada T, Wessagowit V, South AP, et al. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation.J Invest Dermatol,2003,120(3):345-530.
[26]Desmet S, Devos SA, Chan I, et al. Clinical and molecular abnormalities in lipoid proteinosis. Eur J Dermatol,2005,15(5):344-346.
[27]Uchida T, Hayashi H, Inaoki M, etal. A failure of mucocutaneous lymphangiogenesis may underlie the clinical features of lipoid proteinosis. Br J Dermatol,2007,156(1):152-157.
[28]Chan I, Bingewar G, Patil K, et al. An Indian child with lipoid proteinosis resulting from a recurrent frameshift mutation (507delT) in the extracellular matrix protein 1 gene. Br J Dermatol,2004,151(3):726-727.
[29]Lupo I, Cefalu AB, Bongiorno MR, etal. A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily. Br J Dermatol,2005,153(5):1019-1022.
[30]Di Giandomenico S, Masi R, Cassandrini D,et al. Lipoid proteinosis:case report and review of the literature. Acta Otorhinolaryngol Ital,2006,26(3):162-167.
[31]Han B, Zhang X, Liu Q,et al. Homozygous missense mutation in the ECM1 gene in Chinese siblings with lipoid proteinosis. Acta Derm Venereol,2007,87(5):387-389.
[32]Wang CY, Zhang PZ, Zhang FR, etal. New compound heterozygous mutations in a Chinese family with lipoid proteinosis. Br J Dermatol,2006,155(2):470-472.
[33]Chan I, Sethuraman G, Sharma VK, et al. Molecular basis of lipoid proteinosis in two Indian siblings.J Dermatol,2004,31(9):764-766.
[34]Nasir M, Latif A, Ajmal M,et al. A novel homozygous 62-bp insertion in ECM1 causes lipoid proteinosis in a multigeneration Pakistani family. Br J Dermatol,2009,161(3):688-690.
[35]Horev L, Wollina DU, Potikha T. Lipoid proteinosis:identification of two novel mutations in the human ECM-1 gene and lack of genotype-phenotype correlation.Acta Derm Venereol,2009,89(5):528-529.