Clinical and Genetic Characteristics of Primary Juvenile-Onset Open-Angle Glaucoma (JOAG)

Abstract

Juvenile-onset open-angle glaucoma (JOAG) is an autosomal dominant disease characterized by an early age of onset and severely elevated intraocular pressures. Large JOAG pedigrees have been pivotal in genetic linkage analyses that have helped establish the association between JOAG and the myocilin gene (MYOC). Numerous disease-causing MYOC mutations have now been identified, and additional loci on other chromosomes have been linked to JOAG. Ongoing molecular genetic studies on myocilin and the search for new gene defects associated with JOAG may offer new directions in our scientific understanding and clinical management of open-angle glaucoma.

Familial juvenile glaucoma with underlying homozygous p.G61E CYP1B1 mutations

“…In Western populations, heterozygous MYOC mutation is the most common identifiable cause of primary juvenile glaucoma, particularly when it is familial. 4 In this consanguineous Saudi Arabian family with familial primary juvenile glaucoma, the 2 affected siblings harbored homozygosity for p.G61E CYP1B1 mutation, the variant most often associated with severe primary congenital glaucoma in Saudi Arabia, 1,2 whereas analysis of MYOC was negative.…”

Mutations in the CYP1B1 gene may contribute to juvenile-onset open-angle glaucoma

“…2 Juvenile-onset open angle glaucoma (JOAG) is a rare subtype of primary open-angle glaucoma (POAG) and characterized by an early age of onset (ranging between 5 and 35 years of age), severe elevation of intraocular pressure (IOP), and a strong genetic linkage with autosomal dominant inheritance. 3 Many clinicians confer that JOAG is different from common adult-onset glaucoma. 4 In addition, JOAG is distinguished from late congenital glaucoma and other childhood glaucomas by the absence of buphthalmos, Haab's striae and anterior segment dysgenesis.…”

“…4 In addition, JOAG is distinguished from late congenital glaucoma and other childhood glaucomas by the absence of buphthalmos, Haab's striae and anterior segment dysgenesis. 3 To date, at least 14 gene loci (GLC1A-N) have been linked to POAG (OMIM #137760). Among these loci, three genes, MYOC encoding myocilin, OPTN encoding optineurin and the WDR36 gene encoding a protein of unknown function, seem to harbour the mutations that lead to POAG.…”

CYP1B1Mutations are a Major Contributor to Juvenile-Onset Open Angle Glaucoma in Saudi Arabia

“…In Western populations, heterozygous MYOC mutation is considered the most common cause of familial primary juvenile glaucoma. 2 Acharya and colleagues suggested that on rare occasions, mutations in the CYP1B1 may be primarily responsible for JOAG by possible monogenic association in an Indian cohort. 3 Based on these observations, it was suggested that primary congenital glaucoma (PCG) and JOAG are allelic variants of CYP1B1 and that MYOC may act through a biochemical pathway with CYP1B1 acting as a modifier for MYOC.…”