Myocilin and glaucoma: A TIGR by the tail?

In 1997, Stone and 14 colleagues from 7 laboratories reported the identification of a gene (TIGR) associated with juvenile open-angle glaucoma (JOAG). Screening of adults with primary open-angle glaucoma (POAG) revealed that about 4% also carried a mutation of the coding region of this gene. The mutations were found through genetic linkage analysis of families with JOAG. Juvenile open-angle glaucoma was a logical starting point in the search for genetic causes of open-angle glaucoma: it shows a strong autosomal-dominant inheritance pattern, occurs at an early age, demonstrates obvious phenotypic signs (dramatic elevation of intraocular pressure and subsequent optic nerve damage), and is likely to be found in multiple generations as parents of affected children are still living. These factors, however, also serve to distinguish it from adult-onset POAG, which generally has a lower intraocular pressure and a less severe course. The discovery of the actual gene represented a true advance over previous studies that had mapped the gene to a segment of a chromosome but did not identify the specific gene. How the mutant gene causes glaucoma is unknown and is the subject of intense research. To date, 26 mutations in the TIGR gene sequence (the term TIGR has been replaced by the term myocilin, abbreviated MYOC) have been described, all associated with either JOAG or adult-onset POAG. A correlation between specific mutations in MYOC and the clinical course of glaucoma has been found. Not all cases of JOAG or POAG have mutations in the MYOC gene, however, indicating that more discoveries of other genes are yet to come. Arch Ophthalmol. 2000;118:974-978