Ala363Thr Mutation in the Myocilin Gene in Japanese Glaucoma Patients

Abstract

Abstract: : Purpose: Myocilin has been reported as a gene responsible for juvenile onset primary open angle glaucoma (POAG) mapped as the GLC1A locus, many mutations of myocilin gene have been reported worldwide. Some mutations were found not only in patients with juvenile onset POAG, but in patients with late onset POAG and normal tension glaucoma. Kubota et al. (2000) reported some novel sequence variants, Ala363Thr mutation in the myocilin gene is highly probable for disease–causing mutations unrelated Japanese patients in these mutation. We examined the Japanese family with Ala363Thr mutation in the myocilin to establish clinical phenotype. Methods: A 68 y. o. male affected POAG and visual field defect. IOP was almost 30 mmHg with no medication and visual field was grade IV in OD, grade V in OS with Aulhorn–Greve classification. A 61 y. o. sister of proband also affected POAG and visual field defect. Genomic DNA was extracted from peripheral blood in these patients and family according to standard procedures, with informed consent. We performed heteroduplex method to detect mutations in the myocilin gene. Results: Ala363Thr missense mutation in the myocilin gene was detected from proband and his sister. A 38 y. o. Daughter of proband and a 32 y. o. son of sister also have this mutation but they have no typical glaucomatous change, although a little enlargement of disc cupping has seen. Conclusions: Ala363Thr missense mutation may cause of late onset POAG. Prudent progress observation is required for the patient with this mutation of OH. The genetic examination is useful for the early diagnosis and treatment of glaucoma.

Keywords: genetics • mutations • gene screening