Penetrance and phenotype of the Thr377Met Myocilin mutation in a large Finnish family with juvenile- and adult-onset primary open-angle glaucoma.

PURPOSE: To study the role of myocilin (MYOC) as a susceptibility gene for juvenile- and adult-onset open-angle glaucoma (JOAG and POAG, respectively).
METHODS: In a six-generation Finnish family with JOAG and POAG, we performed thorough ophthalmologic characterization (including assessment of the visual fields by Octopus perimetry, nerve-fiber layer thickness by photography, and disc size by Heidelberg tomography) of 51 individuals. The coding region of MYOC was screened for mutations by PCR amplification and direct sequencing.
RESULTS: We detected a C > T transition at codon 377 resulting in a substitution of a threonine residue for methionine (Thr377Met) in the olfactomedin-like domain of myocilin, segregating in the family. Of the 20 individuals heterozygous for the mutation, nine (45%) were glaucomatous and two (10%) had ocular hypertension (OHT). The mean age at diagnosis of glaucoma in these individuals was 34.3 years (range: 14-66 years). Moreover, three of these individuals suffered retinal vein occlusion (RVO) in one eye, while one individual without the mutation had RVO.
CONCLUSION: Our results further support the evidence that the Thr377Met mutation in MYOC may represent a susceptibility allele for glaucoma. These findings may facilitate genetic counseling, and early diagnosis and treatment of glaucoma. The possible interaction of factors contributing to RVO in conjunction with the Thr377Met mutation warrants further investigation.