摘要
目的研究福建省一个大型原发性开角型青光眼(POAG)家系的小梁网糖皮质激素诱导反应蛋白基因(MYOC)突变以及该基因突变与表现型之间的关系。
对象与方法收集到一个包括5代共144人的POAG家系,其中17人被确诊为POAG,1人因大杯盘比被诊断为可疑患者,其余126人无症状。共采集到12份血样,其中3人为POAG患者,1人为可疑患者,其余8人为正常人。3位患者均已行手术治疗,目前眼压控制不理想。方法:(1)抽取12位POAG患者和正常家系成员的外周血3ml。(2)使用Wizard Genomic DNA Purification试剂盒从12位家系成员外周静脉血中提取和纯化基因组DNA。(3)参照文献所报道的引物序列设计3对特异性引物。(4)对12位家系成员基因组DNA使用聚合酶链反应(PCR)技术分段扩增MYOC基因的3个编码外显子区域,然后将PCR产物纯化并进行正向和反向测序。(5)结合患者临床表现对该家系基因突变与临床表现型之间的关系进行分析。
结果(1)在福建省一POAG家系中发现了MYOC基因突变4例,其中3人为POAG患者,1位疑似POAG患者,其余8人为正常人。(2)PCR产物测序发现MYOC基因突变c.G1099A,即Gly367Arg突变,该突变为首次在中国人中发现,导致第367位的甘氨酸突变为精氨酸,从而引起相应蛋白质发生结构与功能改变。
结论该家系表现为常染色体显性遗传伴不完全外显。MYOC基因的Gly367Arg突变可能参与了这个大家系的POAG的发病过程,在这个家系中该突变的表型特点是高眼压、大杯盘比和对外科手术治疗不敏感。MYOC基因突变可引起相应蛋白质的结构及功能发生改变,导致POAG的发生。
Purpose: To search for the MYOC mutation of primary open-angle glaucoma (POAG) in a large family in Fujian Province and to investigate the relationship of the genotype and the phenotype.
Patients: We performed comprehensive ophthalmologic examinations for a primary open-angle glaucoma family of five generations which includes 144 members according to the diagnostic criteria of primary open-angle glaucoma. There are 17 members were confirmed to have POAG , 1 with high cup disc ratio was considered as POAG suspect, and the remaining 126 were asymptomatic. 12 available blood samples were obtained and 3 of them were confirmed to have POAG, 1 was considered as POAG suspect, and the remaining 8 were asymptomatic. All the 3 patients had already accepted surgery therapy and the result is not well.
Methods:(1)3ml blood samples were collected from 12 family members including POAG patients and unaffected members.(2)Genomic DNA was extracted and purified from the peripheral leukocytes by using Wizard Genomic DNA Purification kit.(3)3 paires of specific primers were designed according to the references.(4)Genomic DNA of the 12 family members was amplified using polymerase chain reaction. Then the production was purified and sequenced forward and inverse. ( 5 )Investigate the relationship of the genotype and the phenotype according to the clinical symptoms of the patients.
Results: (1)We identified one MYOC mutation in 4 of 12 family members and 3 of them were confirmed to have POAG, 1 was considered as POAG suspect, and the remaining 8 were asymptomatic.(2)The MYOC gene mutation c.G1099A , Gly367Arg, was detected by sequencing the PCR production. The transition at codon 367 produced the mutation of glycine to arginine and the structural and functional alteration of the corresponding protein.
Conclusions: Gly367Arg mutation of MYOC is likely responsible for the etiology of POAG in this large family. The phenotype of this mutation is characterized by high IOP, high vertical cup-to-disc ratios and insensitivity to surgery. MYOC gene mutation could cause structural and functional alteration of the corresponding protein which is exactly one of the risk factors of POAG.
引文
[1] Quigley HA, Broman AT. 2006 The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol,2006, 90(3):262–267.
[2]葛坚.我国近五年青光眼临床与基础研究进展.中华眼科杂志,2005,41:710-716.
[3] WuDunn D.Genetic basis of glaucoma.Curr Opin Ophthalmol, 2002,13(2):55—60.
[4] Wolfs RC, Klaver CC, Ramrattan RS, van Duijn CM, Hofman A, de Jong PT. Genetic risk of primary open-angle glaucoma. Population-based familial aggregation study. Arch Ophthalmol, 1998,116(12):1640-1645.
[5] Ray K, Mookherjee S. Molecular complexity of primary open angle glaucoma: current concepts. J Genet, 2009,88(4):451-467.
[6] Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, Sunden SL, Nishimura D, Clark AF, Nystuen A, Nichols BE, Mackey DA, Ritch R, Kalenak JW, Craven ER, Sheffield VC. Identification of a gene that causes primary open angle glaucoma. Science, 1997, 275(5300):668-670.
[7] Kubota R, Noda S, Wang Y, Minoshima S, Asakawa S, Kudoh J, Mashima Y, Oguchi Y, Shimizu N. A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping. Genomics, 1997, 41(3):360-369.
[8] Nguyen TD, Chen P, Huang WD, Chen H, Johnson D, Polansky JR. Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells. J Biol Chem, 1998, 273(11):6341-6350.
[9] Allingham RR, Liu Y, Rhee DJ. The genetics of primary open-angle glaucoma: a review. Exp Eye Res, 2009 ,88(4):837-844.
[10] Polansky JR, Fauss DJ, Chen P, Chen H, Lütjen-Drecoll E, Johnson D, Kurtz RM, Ma ZD, Bloom E, Nguyen TD. Cellular pharmacology and molecular biology of thetrabecular meshwork inducible glucocorticoid response gene product.Ophthalmologica, 1997,211(3):126-139.
[11] Bulens F, Merchiers P, Iba?ez-Tallon I, De Vriese A, Nelles L, Claessens F, Belayew A, Collen D. Identification of a multihormone responsive enhancer far upstream from the human tissue-type plasminogen activator gene. J Biol Chem, 1997, 272(1):663-671.
[12] Mukhopadhyay A, Gupta A, Mukherjee S, Chaudhuri K, Ray K. Did myocilin evolve from two different primordial proteins? Mol Vis, 2002, 8:271-279.
[13] Karali A, Russell P, Stefani FH, Tamm ER. Localization of myocilin/trabecular meshwork--inducible glucocorticoid response protein in the human eye. Invest Ophthalmol Vis Sci, 2000,41(3):729-740.
[14] Hewitt AW, Mackey DA, Craig JE. Myocilin allele-specific glaucoma phenotype database. Hum Mutat,2008,29(2):207-211.
[15] Adam MF, Belmouden A, Binisti P, Brézin AP, Valtot F, Béchetoille A, Dascotte JC, Copin B, Gomez L, ChaventréA, Bach JF, Garchon HJ.Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Hum Mol Genet, 1997 ,6(12):2091-2097.
[16] Michels-Rautenstrauss K, Mardin C, Wakili N, Jünemann AM, Villalobos L, Mejia C, Soley GC, Azofeifa J, Ozbey S, Naumann GO, Reis A, Rautenstrauss B.Novel mutations in the MYOC/GLC1A gene in a large group of glaucoma patients.Hum Mutat, 2002 ,20(6):479-480.
[17] Ikezoe T, Takeuchit S, Komatsu N, Okada M, Fukushima A, Ueno H, Koeffler HP, Taguchi H. Identification of a new GLC1A mutation in a sporadic, primary open-angle glaucoma in Japan. Int J Mol Med, 2003,12(2):259-261.
[18] Mukhopadhyay A, Acharya M, Mukherjee S, Ray J, Choudhury S, Khan M, Ray K. Mutations in MYOC gene of Indian primary open angle glaucoma patients. Mol Vis, 2002, 8:442-448.
[19] Challa P, Herndon LW, Hauser MA, Broomer BW, Pericak-Vance MA, Ababio-Danso B, Allingham RR. Prevalence of myocilin mutations in adults with primary open-angle glaucoma in Ghana, West Africa. J Glaucoma,2002,11(5):416-420.
[20]魏雁涛,段山,葛坚等,广州开角型青光眼家系致病基因定位与功能初步研究.中华眼科杂志,2005,4l(12):1068—1075.
[21]卓业鸿,葛坚,郭彦等.我国原发性开角型青光眼患者TIGR基因突变筛选、克隆及序列分析.中华眼科杂志,2000,6(36):416—419.
[22] Gong G, Kosoko-Lasaki O, Haynatzki GR, Wilson MR. Genetic dissection of myocilin glaucoma. Hum Mol Genet, 2004, 13: 91-102.
[23] Sarfarazi M, Child A, Stoilova D, Brice G, Desai T, Trifan OC, Poinoosawmy D, Crick RP. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region. Am J Hum Genet, 1998,62(3):641-652.
[24] Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, Héon E, Krupin T, Ritch R, Kreutzer D, Crick RP, Sarfarazi M. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science, 2002, 295(5557):1077-1079.
[25] Hurst HC. Transcription factors 1: bZIP proteins. Protein Profile, 1995,2(2):101-168.
[26] Lavigne P, Crump MP, GagnéSM, Hodges RS, Kay CM, Sykes BD. Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper. J Mol Biol, 1998,281(1):165-181.
[27] Evans RM, Hollenberg SM. Zinc fingers: gilt by association. Cell, 1988,52(1):1-3.
[28] Li Y, Kang J, Horwitz MS. Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains. Mol Cell Biol, 1998,18(3):1601-1610.
[29] Fuse N, Takahashi K, Akiyama H, Nakazawa T, Seimiya M, Kuwahara S, Tamai M. Molecular genetic analysis of optineurin gene for primary open-angle and normal tension glaucoma in the Japanese population. J Glaucoma, 2004,13(4):299-303.
[30]陈建华,徐亮等.原发性开角型青光眼视神经病变诱导反应蛋白基因突变的研究.中华医学杂志,2004, 84(13):1098-1102.
[31] Chalasani ML, Radha V, Gupta V, Agarwal N, Balasubramanian D, Swarup G. A glaucoma-associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. Invest Ophthalmol Vis Sci, 2007 ,48(4):1607-1614.
[32] Fenner BJ, Scannell M, Prehn JH. Identification of polyubiquitin binding proteins involved in NF-kappaB signaling using protein arrays. Biochim Biophys Acta, 2009 ,1794(7):1010-1016.
[33] Park BC, Shen X, Samaraweera M, Yue BY. Studies of optineurin, a glaucoma gene: Golgi fragmentation and cell death from overexpression of wild-type and mutant optineurin in two ocular cell types. Am J Pathol, 2006,169(6):1976-1989.
[34] Monemi S, Spaeth G, DaSilva A, Popinchalk S, Ilitchev E, Liebmann J, Ritch R, Héon E, Crick RP, Child A, Sarfarazi M. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1. Hum Mol Genet, 2005,14(6):725-733.
[35] Hauser MA, Allingham RR, Linkroum K, Wang J, LaRocque-Abramson K, Figueiredo D, Santiago-Turla C, del Bono EA, Haines JL, Pericak-Vance MA, Wiggs JL. Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma. est Ophthalmol Vis Sci, 2006 ,47(6):2542-2546.
[36] Pasutto F, Mardin CY, Michels-Rautenstrauss K, Weber BH, Sticht H, Chavarria-Soley G, Rautenstrauss B, Kruse F, Reis A. Profiling of WDR36 missense variants in German patients with glaucoma. Invest Ophthalmol Vis Sci, 2008,49(1):270-274.
[37] Miyazawa A, Fuse N, Mengkegale M, Ryu M, Seimiya M, Wada Y, Nishida K. Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese. Mol Vis, 2007,13:1912-1919.
[38] Fan BJ, Wang DY, Cheng CY, Ko WC, Lam SC, Pang CP. Different WDR36 mutation pattern in Chinese patients with primary open-angle glaucoma. Mol Vis, 2009,15:646-653.
[39] Footz T. K., Johnson J. L., Dubois S.,et al. Glaucoma-associated WDR36 variantsencode functional defects in a yeast model system. Hum Mol Genet,2009, 18:1276–1287.
[40]Bernstein, K.A., Gallagher,et al. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell, 2004,3:1619–1626.
[41] Gallenberger M, Meinel DM, Kroeber M, et al. Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro. Hum Mol Genet, 2011,20(3):422-35.
[42] Ray K, Mookherjee S. Molecular complexity of primary open angle glaucoma: current concepts. J Genet, 2009 ,88(4):451-467.
[43] Ju JW, Kim SJ, Jun CD, Chun JS. p38 kinase and c-Jun N-terminal kinase oppositely regulates tumor necrosis factor alpha-induced vascular cell adhesion molecule-1 expression and cell adhesion in chondrosarcoma cells. IUBMB Life, 2002 ,54(5):293-299.
[44] Quigley HA. Number of people with glaucoma worldwide: Br J Ophthalmol. 1996 May;80(5):389-93.
[45] Fuse N. Genetic bases for glaucoma: Tohoku J Exp Med. 2010;221(1):1-10.
[46] Quigley HA, Vitale S. Models of open angle glaucoma prevalence and incidence in the United States: Invest Ophthalmol Vis Sci.1997; 38:83-91.
[47] WuDurm D.Genetic basis ofglaucoma.Curr Opin Ophthalmol,2002,13:55—60.
[48] Foster PJ, Oen FT, Machin D, Ng TP, Devereux JG, Johnson GJ, Khaw PT, Seah SK. The prevalence of glaucoma in Chinese residents of Singapore: a cross-sectional population survey of the Tanjong Pagar district:Arch Ophthalmol. 2000 Aug;118(8):1105-11.
[49] Sheffield VC, Stone EM, Alward WL, Drack AV, Johnson AT,Streb LM, Nichols BE. Genetic linkage of familial open angle glaucoma to chromosome 1q21-q31:Nat Genet .1993; 4:47-50.
[50] Stoilova D, Child A, Trifan OC, Crick RP, Coakes RL, Sarfarazi M. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region: Genomics.1996;36:142-50.
[51] Wirtz MK, Samples JR, Kramer PL, Rust K, Topinka JR, Yount J, Koler RD,Acott TS. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q: Am J Hum Genet. 1997; 60:296-304.
[52] Trifan OC, Traboulsi EI, Stoilova D, Alozie I, Nguyen R, Raja S, Sarfarazi M. A third locus (GLC1D) for adult-onset primary open-angle glaucoma maps to the 8q23 region: Am J Ophthalmol. 1998 Jul;126(1):17-28.
[53] Sarfarazi M, Child A, Stoilova D, Brice G, Desai T, Trifan OC, Poinoosawmy D, Crick RP. Localization of the fourth locus(GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region: Am J Hum Genet. 1998; 62:641-52.
[54] Wirtz MK, Samples JR, Rust K, Lie J, Nordling L, Schilling K,Acott TS, Kramer PL. GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36: Arch Ophthalmol. 1999;117:237-41.
[55] Wiggs JL, Lynch S, Ynagi G, Maselli M, Auguste J, Del Bono EA, Olson LM, Haines JL. A genomewide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12: Am J Hum Genet. 2004 Jun;74(6):1314-20.
[56] Monemi S, Spaeth G, DaSilva A, Popinchalk S, Ilitchev E, Liebmann J, Ritch R, Héon E, Crick RP, Child A, Sarfarazi M. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1: Hum Mol Genet. 2005 Mar 15;14(6):725-33.
[57] Allingham RR, Wiggs JL, Hauser ER, Larocque-Abramson KR, Santiago-Turla C, Broomer B, Del Bono EA, Graham FL, Haines JL, Pericak-Vance MA, Hauser MA. Early adult-onset POAG linked to 15q11-13 using ordered subset analysis: Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2002-5.
[58] Baird PN, Foote SJ, Mackey DA, Craig J, Speed TP, Bureau A. Evidence for a novel glaucoma locus at chromosome 3p21-22: Hum Genet. 2005 Jul;117(2-3):249-57.
[59] Woodroffe A, Krafchak CM, Fuse N, Lichter PR, Moroi SE, Schertzer R, Downs CA, Duren WL, Boehnke M, Richards JE. Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis: Exp Eye Res. 2006 Jun;82(6):1068-74.
[60] Pang CP, Fan BJ, Canlas O, Wang DY, Dubois S, Tam PO, Lam DS, Raymond V,Ritch R. A genome-wide scan maps a novel juvenile-onset primary open angle glaucoma locus to chromosome 5q: Mol Vis. 2006; 12:85-92.
[61] Wang DY, Fan BJ, Chua JK, Tam PO, Leung CK, Lam DS,Pang CP. A genome-wide scan maps a novel juvenile-onset primary open-angle glaucoma locus to 15q: Invest Ophthalmol Vis Sci. 2006; 47:5315-21.
[62] Suriyapperuma SP, Child A, Desai T, Brice G, Kerr A, Crick RP, Sarfarazi M. A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15-p16 region: Arch Ophthalmol. 2007 Jan;125(1):86-92.
[63] Gong G, Kosoko-Lasaki O, Haynatzki GR, Wilson MR. Genetic dissection of myocilin glaucoma: Hum Mol Genet. 2004; 13 Spec No 1:R91-102.
[64] Stone EM, Fingert JH, Alward WL, et al. Identification of a gene that causes primary open angle glaucoma: Science. 1997;275:668–670.
[65] Alward WL, Fingert JH, Coote MA, et al. Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A): N Engl J Med. 1998;338:1022–1027.
[66] Pang CP, Leung YF, Fan B, Baum L, Tong WC, Lee WS, Chua JK, Fan DS, Liu Y, Lam DS. TIGR/MYOC gene sequence alterations in individuals with and without primary open angle glaucoma: Invest Ophthalmol Vis Sci. 2002; 43:3231-5.
[67] Bruttini M, Longo I, Frezzotti P, Ciappetta R, Randazzo A,Orzalesi N, Fumagalli E, Caporossi A, Frezzotti R, Renieri A. Mutations in the myocilin gene in families with primary open-angle glaucoma and juvenile open-angle glaucoma: Arch Ophthalmol. 2003; 121:1034-8.
[68] Fingert JH, Heon E, Liebmann JM, Yamamoto T, Craig JE, Rait J, Kawase K, Hoh ST, Buys YM, Dickinson J, Hockey RR, Williams-Lyn D, Trope G, Kitazawa Y, Ritch R, Mackey DA, Alward WL, Sheffield VC, Stone EM. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations:Hum Mol Genet. 1999; 8:899-905.
[69] Jacobson N,Andresws M,Shepard AR,et a1.Non—secretion of mutant proteins of the glaucoma gene Myocilin in cultured trabecular meshwork cells and in aqueoushumor.Hum Mol Genet2001;10:117—125.
[70] Joe MK, Sohn S,Hur W,et a1.Accumulation of mutant myocilins in ER leads to ER stress and potential cytotoxicity in human trabecular meshwork cells.Biochem Biophys Res Commun 2003;312:592-600.
[71] Kwon HS, Lee HS, Ji Y, Rubin JS, Tomarev SI. Myocilin is a modulator of Wnt signaling. Mol Cell Biol,2009 ,29(8):2139-2154.
[72] Shen X, Koga T, Park BC, SundarRaj N, Yue BY. Rho GTPase and cAMP/protein kinase A signaling mediates myocilin-induced alterations in cultured human trabecular meshwork cells. J Biol Chem, 2008,283(1):603-612.
[73] Lindsey JD, Gaton DD, Sagara T, Polansky JR, Kaufman PL, Weinreb RN. Reduced TIGR/myocilin protein in the monkey ciliary muscle after topical prostaglandin F(2alpha) treatment. Invest Ophthalmol Vis Sci, 2001,42(8):1781-1786.
[74] Fautsch MP, Bahler CK, Jewison DJ, Johnson DH. Recombinant TIGR/MYOC increases outflow resistance in the human anterior segment. Invest Ophthalmol Vis Sci, 2000,41(13):4163-4168.
[75] Karali A, Russell P, Stefani FH, Tamm ER. Localization of myocilin/trabecular meshwork--inducible glucocorticoid response protein in the human eye. Invest Ophthalmol Vis Sci, 2000,41(3):729-740.
[76] Tomarev SI, Nakaya N. Olfactomedin domain-containing proteins: possible mechanisms of action and functions in normal development and pathology. Mol Neurobiol, 2009 ,40(2):122-138.
[77] Jia LY, Gong B, Pang CP, Huang Y, Lam DS, Wang N, Yam GH. Correction of the disease phenotype of myocilin-causing glaucoma by a natural osmolyte. Invest Ophthalmol Vis Sci, 2009 ,50(8):3743-3749.
[78] Resch ZT, Fautsch MP. Glaucoma-associated myocilin: a better understanding but much more to learn. Exp Eye Res, 2009 ,88(4):704-712.
[79] He Y, Leung KW, Zhuo YH, Ge J. Pro370Leu mutant myocilin impairs mitochondrial functions in human trabecular meshwork cells. Mol Vis, 2009,15:815-825.
[80] Joe MK, Sohn S, Choi YR, Park H, Kee C. Identification of flotillin-1 as aprotein interacting with myocilin: implications for the pathogenesis of primary open-angle glaucoma. Biochem Biophys Res Commun, 2005, 336(4):1201-1206.
[81] Peters DM, Herbert K, Biddick B, Peterson JA. Myocilin binding to Hep II domain of fibronectin inhibits cell spreading and incorporation of paxillin into focal adhesions. Exp Cell Res, 2005, 303(2):218-228.
[82] Polansky JR,Fauss DJ,Zimmerman CC.Regulation of TIGR/MYOC gene expression in human trabecular meshwork cells.Eye 2002;14:503-514.
[83] Gobeil S,Rodrigue MA,Moisan S,et a1.IntraceLLuLar sequestration of hetero-oligomers formed by wild-type and glaucoma—causingmyoci2 lin mutants.Invest Ophthalmol Vis Sci,2004.45(1 0):3560·3567.
[84] Wirtz MK, Samples JR, Toumanidou V, Charlesworth J, Mikropoulos DG, Kaltsos K, Economou A, Dimopoulos A, Georgiadou IN, Moumtzis G, Papanastasiou A, Kramer PL, Dyer T, Blangero J, Konstas AG. Association of POAG risk factors and the Thr377Met MYOC mutation in an isolated Greek population: Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3055-60.
[85] Avisar I, Lusky M, Robinson A, Shohat M, Dubois S, Raymond V, Gaton DD. The novel Y371D myocilin mutation causes an aggressive form of juvenile open-angle glaucoma in a Caucasian family from the Middle-East: Mol Vis. 2009 Sep 24;15:1945-50.
[86] Zhuo YH, Wei YT, Bai YJ, Duan S, Lin MK, Saragovi HU, Ge J. Pro370Leu MYOC gene mutation in a large Chinese family with juvenile-onset open angle glaucoma: correlation between genotype and phenotype: Mol Vis. 2008 Aug 22;14:1533-9.
[87] Kanagavalli J, Krishnadas SR, Pandaranayaka E, Krishnaswamy S, Sundaresan P. Evaluation and understanding of myocilin mutations in Indian primary open angle glaucoma patients: Mol Vis. 2003; 9:606-14.
[88] Cobb CJ, Scott G, Swingler RJ, Wilson S, Ellis J, MacEwen CJ, McLean WH. Rapid mutation detection by the transgenomic wave analyser DHPLC identifies MYOC mutations in patients with ocular hypertension and/or open angle glaucoma: Br JOphthalmol. 2002; 86:191-5.
[89] Kanagavalli J, Pandaranayaka PJ, Krishnadas SR, Krishnaswamy S, Sundaresan P. In vitro and in vivo study on the secretion of the Gly367Arg mutant myocilin protein: Mol Vis. 2007 Jul 13;13:1161-8.
1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020.Br J Ophthalmol, 2006, 90(3):262-7.
2.葛坚.我国近五年青光眼临床与基础研究进展.中华眼科杂志,2005,41:710-716.
3.WuDunn D.Genetic basis of glaucoma.Curr Opin Ophthalmol, 2002,13:55-60.
4. Ray K, Mookherjee S.Molecular complexity of primary open angle glaucoma:current concepts. J Genet, 2009, 88(4):451-67.
5.Hewitt AW, Mackey DA, Craig JE. Myocilin allele-specific glaucoma phenotype database. Hum Mutat, 2008,29(2):207-211.
6.Monemi S,Spaeth G,Dasilva A,et a1.Identification of a novel adult—onset primary open-angle glaucoma(POAG)gene on 5q22.1.Hum Mol Genet,2005,14:725-733.
7. Hauser MA, Allingham RR, Linkroum K,et al. Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci, 2006, 47(6):2542-6.
8. Weisschuh N., Wolf C., Wissinger B., et al. Variations in the WDR36 gene in German patients with normal tension glaucoma. Mol Vis,2006, 13:724–729.
9. Pasutto F., Mardin C. Y., Michels-Rautenstrauss K., et al. Profiling of WDR36 missense variants in German patients with glaucoma. Invest Ophthalmol Vis Sci,2008, 49:270–274.
10. Hewitt A. W., Dimasi D. P., Mackey D. A., et al. A glaucoma case-control study of the WDR36 gene D658G sequence variant. Am J Ophthalmol,2006, 142:324–325.
11. Fingert J. H., Alward W. L., Kwon Y. H., et al. No association between variations in the WDR36 gene and primary open-angle glaucoma. Arch Ophthalmol, 2007,125: 434–436.
12. Frezzotti P, Pescucci C, Papa FT, et al. Association between primary open-angle glaucoma (POAG) and WDR36 sequence variance in Italian families affected byPOAG. Br J Ophthalmol, 2010[Epub ahead of print]
13. Motushchuk AE, Komarova TIu, Grudinina NA, et al. Genetic variants of CYP1B1 and WDR36 in the patients with primary congenital glaucoma and primary open angle glaucoma from Saint-Petersburg. Genetika, 2009, 45(12):1659-67.
14. Fan B. J., Wang D. Y., Cheng C. Y.,et al. Different WDR36 mutation pattern in Chinese patients with primary open-angle glaucoma. Mol Vis,2009, 15: 646–653.
15. Miyazawa A., Fuse N.,Mengkegale M., et al. Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese. Mol Vis,2007, 13:1912–1919.
16. Footz T. K., Johnson J. L., Dubois S.,et al. Glaucoma-associated WDR36 variantsencode functional defects in a yeast model system. Hum Mol Genet,2009, 18: 1276–1287.
17.Bernstein, K.A., Gallagher,et al. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell, 2004,3:1619–1626.
18. Gallenberger M, Meinel DM, Kroeber M, et al. Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro. Hum Mol Genet, 2011,20(3):422-35.
19. Skarie J. M. ,Link B. A. The primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway. Hum Mol Genet, 2008,17:2474–2485.
20. Chi ZL, Yasumoto F, Sergeev Y,et al.Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice. Hum Mol Genet, 2010 ,19(19):3806-15.
21.Skarie, J.M. Link, B.A. The primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway. Hum Mol Genet, 2008, 17: 2474–2485.
22. Park BC, Tibudan M, Samaraweera M,et al. Interaction between two glaucoma genes, optineurin and myocilin. Genes Cells ,2007,12:969-79.
23. Pang C. P., Fan B. J., Canlas O., et al. A genome-wide scan maps a novel juvenile-onset primary open angle glaucoma locus to chromosome 5q. Mol Vis,2006,12: 85–92.