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 primary open-angle glaucoma, 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 genes 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 the MYOC gene 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 MYOC protein. This substitution may cause structural and functional changes of the protein based on bioinformatics analysis. No mutations were found in CYP1B1 gene.
Conclusions Our study suggests that the novel mutation D384G of MYOC is likely responsible for the pathogenesis of POAG in this pedigree.
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