Analysis of Myocilin Mutations in 1703 Glaucoma Patients From Five Different Populations

Abstract

A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.

Molecular genetic basis of primary inherited optic neuropathies

“…However, these loci and genes may account for only a small proportion of glaucoma seen in the general population. Studies of MYOC and OPTN mutations in the general glaucoma population have shown that they account for 3.4% of open angle glaucoma 65 and up to 15% of NTG, 64 respectively. The association of two intronic OPA1 polymorphisms in the OPA1 gene with normal tension glaucoma (IVS8 þ 4C/T and IVS8 þ 32T/C), 66,67 is of interest since NTG may account for 20-50% of open angle glaucoma.…”

Prevalence of myocilin gene mutations in a novel UK cohort of POAG patients

“…5,6 Over 70 mutations have subsequently been identified by numerous other groups; [7][8][9][10] however, this is a small fraction of the total number of patients affected with POAG. The extremely high prevalence of POAG in the general population means that this represents several tens of thousands of patients in the United Kingdom.…”

Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells

“…Mutations in the olfactomedin domain may be deleterious for the functions of these proteins. For example, mutations in the olfactomedin domain of the human MYOCILIN gene may lead to juvenile open-angle glaucoma and in some cases to adult onset glaucoma [17][18][19][20].…”