Evaluating the Role of Myocilin and Optineurin Genes in Familial Primary Open Angle Glaucoma

Abstract

Purpose: : To determine the role of myocilin and optineurin genes in the pathogenesis of primary open angle glaucoma in a large pedigree with autosomal dominant disease from South India.

Methods: : Each member of the pedigree received an ophthalmic exam from one of the authors and contributed a DNA sample for study. DNA samples from the family members with POAG were tested for disease-causing mutations in the myocilin and optineurin genes using a combination of restriction fragment length polymorphism (RFLP) analysis and bi-directional DNA sequencing.

Results: : A total of 76 family members were studied. Thirteen were diagnosed with POAG, ten were judged to be POAG suspects, and 53 did not meet criteria for either diagnosis. No disease-causing mutations were detected in myocilin or optineurin.

Conclusions: : Mutations in myocilin or optineurin are the most common known cause of autosomal dominant POAG. The absence of mutations in the genes that are currently known to cause POAG strongly suggests that the disease in this pedigree is caused by a novel glaucoma gene. Linkage analysis and next generation DNA sequencing are being used to identify this gene.

Keywords: genetics • intraocular pressure • candidate gene analysis