The mutational spectrum of Myocilin gene among familial versus sporadic cases of Juvenile onset open angle glaucoma.
Gupta Viney, Somarajan Bindu I, Gupta Shikha, Walia Gagandeep Kaur, Singh Abhishek, Sofi Rayees, Chaudhary Richard Sher, Sharma Arundhati
AI Summary
Studying JOAG, researchers found MYOC mutations are significantly more common in familial (27%) than sporadic (2%) cases, suggesting genetic screening is best focused on familial JOAG.
Abstract
Purpose
Juvenile onset primary open angle glaucoma (JOAG) is a rare disorder associated with high IOP and progressive optic neuropathy in patients diagnosed before the age of 40 years. While in some populations it has primarily an autosomal dominant pattern of inheritance, in others it occurs in a primarily sporadic form. The main aim of the study was to assess the relative prevalence of Myocilin (MYOC) mutations in familial versus sporadic cases of JOAG.
Methods
We screened 92 unrelated (sporadic) JOAG patients, and 22 affected families (70 affected members and 36 unaffected) for variations in the MYOC gene. We also analyzed the clinical features associated with these variations.
Results
Three coding sequence variants were identified as mutations causing JOAG. Four families segregated distinct mutations at Gly367Arg, and two families at Gln337Arg, while only two sporadic JOAG cases harbored MYOC mutations (Gly367Arg and Gln48His). The frequency of MYOC mutations in familial cases (27%) was significantly higher than in sporadic JOAG cases (2%); p = 0.001. A 90% penetrance for the Gly367Arg variant was seen by the age of 40 years in our patients. Characteristic allele signatures, indicative of specific founder effects, were not observed for the Gly367Arg mutation that was looked for in 12 patients among 2 geographically close families, which harbored this mutation.
Conclusion
Our data demonstrated that genetic screening for MYOC mutations should be focused toward cases with familial rather than sporadically occurring JOAG.
MeSH Terms
Shields Classification
Key Concepts6
Three coding sequence variants of the Myocilin (MYOC) gene were identified as mutations causing Juvenile onset primary open angle glaucoma (JOAG).
The frequency of Myocilin (MYOC) mutations in familial cases of Juvenile onset primary open angle glaucoma (JOAG) was 27%, which was significantly higher than in sporadic JOAG cases (2%) (p = 0.001).
Four families with Juvenile onset primary open angle glaucoma (JOAG) segregated distinct Myocilin (MYOC) mutations at Gly367Arg, and two families segregated mutations at Gln337Arg.
Only two sporadic Juvenile onset primary open angle glaucoma (JOAG) cases harbored Myocilin (MYOC) mutations (Gly367Arg and Gln48His).
A 90% penetrance for the Myocilin (MYOC) Gly367Arg variant was observed by the age of 40 years in patients with Juvenile onset primary open angle glaucoma (JOAG).
Genetic screening for Myocilin (MYOC) mutations should be focused toward cases with familial rather than sporadically occurring Juvenile onset primary open angle glaucoma (JOAG).
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