Common and Rare Genetic Risk Factors for Glaucoma

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity

“…Indeed, PCG accounts for 18% of children enrolled in institutions for the blind worldwide (7). PCG occurs in all ethnic groups, but the disease incidence varies according to ethnic background, ranging from 1:1,250 in inbred populations to 1:30,000 in populations with heterogeneous ethnicity (6,(8)(9)(10)(11)(12). Families can exhibit autosomal recessive or dominant inheritance, although the majority of cases appear to be sporadic (5,6,(10)(11)(12)(13)(14).…”

“…The molecular etiology of PCG is only partially understood, as only a few genes responsible for PCG have been identified (6,(10)(11)(12)(13)(14). Mutations in CYP1B1, which encodes a cytochrome P450 enzyme, is the most common cause of autosomal recessive PCG worldwide, accounting for up to 87% of familial cases in some inbred populations but only 25%-27% in populations with heterogeneous ethnicity (5, 9, 15-18).…”

Genetics of Primary Inherited Disorders of the Optic Nerve: Clinical Applications

“…Mutations in early-onset glaucoma genes can cause AD or AR disease: CYP1B1 and LTBP2 cause AR disease, whereas mutations in FOXC1, PITX2, PAX6, MYOC, and OPTN all cause glaucoma inherited as a dominant trait (Wang and Wiggs 2014). Phenotypically, disease caused by mutations in these genes can have similar clinical features making it difficult to make a genetic diagnosis by clinical examination alone.…”

“…Eight genes are currently known to cause earlyonset (before age 40) glaucoma with autosomal recessive (AR) or autosomal dominant (AD) inheritance (Wang and Wiggs 2014). Approximately 20% of patients ascertained with earlyonset glaucoma through tertiary care facilities will have mutations in one of the genes known to cause early-onset glaucoma (Fig.…”

“…Phenotypically, NTG can share clinical features with the inherited optic neuropathies. Glaucoma with onset before age 40 (early-onset) can be inherited as Mendelian autosomal recessive or autosomal dominant traits, whereas adult onset disease has complex inheritance (Wang and Wiggs 2014).…”