A Novel MYOC Heterozygous Mutation Identified in a Chinese Uygur Pedigree with Primary Open-angle Glaucoma

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2012 Aug 10

PMID 22876119

Citations 4

Authors

Su-Ping Cai

Paerheti Muhemaiti

Yan Yin

Hongbo Cheng

A Di Ya

Maliyamu Keyimu

Xu Cao

Ning Fan

Liqiong Jiang

Naihong Yan

Xiaomin Zhou

Yun Wang

Xuyang Liu

Affiliations

Soon will be listed here.

Abstract

Purpose: To characterize the clinical features of a Chinese Uygur pedigree with primary open-angle glaucoma (POAG) and to identify mutations in two candidate genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and human dioxin-inducible cytochrome P450 (CYP1B1).

Methods: Twenty one members from a Chinese Uygur family of four generations were included in the study. All participants underwent complete ophthalmologic examinations. Five were diagnosed as POAG, four as glaucoma suspects, and the rest were asymptomatic. Molecular genetic analysis was performed on all subjects included in the study. All exons of CYP1B1 and MYOC were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. The variations detected were evaluated in available family members as well as 102 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis.

Results: Elevated intraocular pressure and late-stage glaucomatous cupping of the optic disc were found in five patients of this family. A novel heterozygous missense mutation c.1151 A>G in exon 3 of MYOC was found in all five patients diagnosed as POAG and four glaucoma suspects, but not in the rest of the family members and 102 normal controls. This mutation caused an amino acid substitution of aspartic acid to glycine at position 384 (p. D384G) of the MYOC protein. This substitution may cause structural and functional changes of the protein based on bioinformatics analysis. No mutations were found in CYP1B1.

Conclusions: Our study suggests that the novel mutation D384G of MYOC is likely responsible for the pathogenesis of POAG in this pedigree.

Citing Articles

Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?.

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Research progress on human genes involved in the pathogenesis of glaucoma (Review).

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Haplotype analysis of association of the MYOC gene with primary angle-closure glaucoma in a Han Chinese population.

Jin X, Wang D, Qu L, Hou B, Gong Y, Xu W Genet Test Mol Biomarkers. 2014; 19(1):3-8.

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The nerve growth factor signaling and its potential as therapeutic target for glaucoma.

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References

Vincent A, Billingsley G, Buys Y, Levin A, Priston M, Trope G . Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet. 2002; 70(2):448-60. PMC: 384919. DOI: 10.1086/338709. View

Kanagavalli J, Krishnadas S, 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. View

Zhao X, Yang C, Tong Y, Zhang X, Xu L, Li Y . Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma. Mol Vis. 2010; 16:1728-35. PMC: 2927375. View

Tamm E, Russell P . The role of myocilin/TIGR in glaucoma: results of the Glaucoma Research Foundation catalyst meeting in Berkeley, California, March 2000. J Glaucoma. 2001; 10(4):329-39. DOI: 10.1097/00061198-200108000-00014. View

Fan B, Leung D, Wang D, Gobeil S, Raymond V, Tam P . Novel myocilin mutation in a Chinese family with juvenile-onset open-angle glaucoma. Arch Ophthalmol. 2006; 124(1):102-6. DOI: 10.1001/archopht.124.1.102. View

Kennan A, Mansergh F, Fingert J, Clark T, Ayuso C, Kenna P . A novel Asp380Ala mutation in the GLC1A/myocilin gene in a family with juvenile onset primary open angle glaucoma. J Med Genet. 1998; 35(11):957-60. PMC: 1051493. DOI: 10.1136/jmg.35.11.957. View

Pang C, Leung Y, Fan B, Baum L, Tong W, Lee W . TIGR/MYOC gene sequence alterations in individuals with and without primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2002; 43(10):3231-5. View

Shimizu S, Lichter P, Johnson A, Zhou Z, Higashi M, Gottfredsdottir M . Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma. Am J Ophthalmol. 2000; 130(2):165-77. DOI: 10.1016/s0002-9394(00)00536-5. View

Cobb C, Scott G, Swingler R, Wilson S, Ellis J, MacEwen C . Rapid mutation detection by the transgenomic wave analyser DHPLC identifies MYOC mutations in patients with ocular hypertension and/or open angle glaucoma. Br J Ophthalmol. 2002; 86(2):191-5. PMC: 1771000. DOI: 10.1136/bjo.86.2.191. View

10.

Ge J, Zhuo Y, Guo Y, Ming W, Yin W . Gene mutation in patients with primary open-angle glaucoma in a pedigree in China. Chin Med J (Engl). 2002; 113(3):195-7. View

11.

Taniguchi F, Suzuki Y, Shirato S, Araie M . The Gly367Arg mutation in the myocilin gene causes adult-onset primary open-angle glaucoma. Jpn J Ophthalmol. 2000; 44(4):445-8. DOI: 10.1016/s0021-5155(00)00201-x. View

12.

GOLDWYN R, Waltman S, Becker B . Primary open-angle glaucoma in adolescents and young adults. Arch Ophthalmol. 1970; 84(5):579-82. DOI: 10.1001/archopht.1970.00990040581004. View

13.

Suzuki Y, Shirato S, Taniguchi F, Ohara K, Nishimaki K, Ohta S . Mutations in the TIGR gene in familial primary open-angle glaucoma in Japan. Am J Hum Genet. 1997; 61(5):1202-4. PMC: 1716051. DOI: 10.1086/301612. View

14.

Melki R, Colomb E, Lefort N, Brezin A, Garchon H . CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma. J Med Genet. 2004; 41(9):647-51. PMC: 1735887. DOI: 10.1136/jmg.2004.020024. View

15.

Mabuchi F, Yamagata Z, Kashiwagi K, Ishijima K, Tang S, Iijima H . A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein. J Hum Genet. 2001; 46(2):85-9. DOI: 10.1007/s100380170114. View

16.

Quigley H . Number of people with glaucoma worldwide. Br J Ophthalmol. 1996; 80(5):389-93. PMC: 505485. DOI: 10.1136/bjo.80.5.389. View

17.

Stone E, Fingert J, Alward W, Nguyen T, Polansky J, Sunden S . Identification of a gene that causes primary open angle glaucoma. Science. 1997; 275(5300):668-70. DOI: 10.1126/science.275.5300.668. View

18.

Booth A, Churchill A, Anwar R, Menage M, Markham A . The genetics of primary open angle glaucoma. Br J Ophthalmol. 1997; 81(5):409-14. PMC: 1722199. DOI: 10.1136/bjo.81.5.409. View

19.

Lopez-Garrido M, Sanchez-Sanchez F, Lopez-Martinez F, Aroca-Aguilar J, Blanco-Marchite C, Coca-Prados M . Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma. Mol Vis. 2006; 12:748-55. View

20.

Bagiyeva S, Marfany G, Gonzalez-Angulo O, Gonzalez-Duarte R . Mutational screening of CYP1B1 in Turkish PCG families and functional analyses of newly detected mutations. Mol Vis. 2007; 13:1458-68. View