In general, the early-onset forms of glaucoma are rare and often follow patterns of simple Mendelian inheritance with mutations that are highly penetrant. Previously, genes with such disease-causing mutations were identified by linkage analysis in large, multigenerational families that show either autosomal dominant or autosomal recessive patterns of inheritance. Current approaches using whole-exome sequencing can successfully identify disease genes using smaller families without evidence of linkage. Genetic regions associated with glaucoma are named according to the type of glaucoma—GLC1 for open-angle glaucoma, GLC2 for angle-closure glaucoma, and GLC3 for congenital glaucoma—followed by a letter to indicate the sequence of discovery: GLC1A, GLC1B, GLC1C, and so on. Table 1-2 lists the important genes associated with glaucoma, for which genetic testing may be of clinical utility.
Table 1-2 Clinically Impor tant Glaucoma Loci
Juvenile Open-Angle Glaucoma
Juvenile open-angle glaucoma (JOAG) is defined by having an onset before 40 years of age, an open anterior chamber angle, and an absence of secondary features. The myocilin gene (MYOC, formerly known as trabecular meshwork–inducible glucocorticoid response, or TIGR, within the initial larger chromosomal region of GLC1A) was the first glaucoma gene discovered. Autosomal dominant disease-causing mutations in MYOC account for up to 36% of cases of JOAG and 4% of POAG. There is evidence that mutant myocilin accumulates in cells rather than being secreted, possibly resulting in toxicity to the trabecular meshwork.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.