A Recurrent G367R Mutation in Associated with Juvenile Open Angle Glaucoma in a Large Chinese Family

Aim: To identify the mutations of , , and in a large Chinese family affected by juvenile open angle glaucoma (JOAG).

Methods: Of 114 members of one family were recruited in this study. Blood samples from twelve members of this pedigree were collected for further research. As a control, 100 unrelated subjects were recruited from the same hospital. The exon and flanking intron sequences of candidate genes were amplified using the polymerase chain reaction and direct DNA sequencing.

Results: The proband (III:10) was a seventy-three years old woman with binocular JOAG at the age of 31. A recurrent heterozygous mutation (c.1099G>A) of was identified in the three JOAG patients and another suspect. This transition was located in the first base pair of codon 367 (GGA>AGA) in exon 3 of and was predicted to be a missense substitution of glycine to arginine (p.G367R) in myocilin. Mutations in , or were not detected in this study. The G367R mutation was not present in unaffected family members or in 100 ethnically matched controls. Other variants of the coding regions of candidate genes were not detected in all participants. To date, this family was the largest to have been identified as carrying a certain mutation in China, further evidence of a founder effect for the G367R mutant was provided by our data.

Conclusion: A c.1099G>A mutation in an autosomal dominant JOAG family is identified and the characteristic phenotypes among the patients are summarized. Genetic testing could be utilized in high-risk populations and be helpful not only for genetic counseling, but also for early diagnosis and treatment of affected patients or carriers of inherited JOAG.