Penetrance of Myocilin Mutations—Who Gets Glaucoma?

Mutations in the myocilin (MYOC) gene were discovered as a cause of primary open-angle glaucoma (POAG) in 1997.¹ Twenty-one years later, mutations in MYOC remain the most common molecularly defined cause of glaucoma and are responsible for 3% to 4% of adult-onset POAG cases.² Glaucoma associated with MYOC is transmitted with autosomal dominant inheritance³; offspring from parents with glaucoma caused by a MYOC mutation have a 50% chance of inheriting the mutation and increased risk for glaucoma. The most common glaucoma-associated MYOC mutation is a nonsense mutation, Gln368Stop, that produces truncated MYOC protein that is missing its last quarter.² This mutation has been detected in 1.6% of patients with POAG in large case-control studies and is responsible for more glaucoma than any other known mutation.² In their article in JAMA Ophthalmology, Han et al⁴ evaluated very large study populations to investigate just how high the risk for glaucoma is for those with this MYOC mutation.