title: Low prevalence of MYOC mutations in UK primary open-angle glaucoma patients limits the utility of genetic testing.
abstract: Primary open angle glaucoma (POAG) affects 1% of people over age 40. Early detection and treatment can prevent blindness, but the disease is often asymptomatic until a late stage. Positive family history is an important risk factor and previous studies indicate that approximately 5% of POAG results from mutations in the myocilin ( MYOC) gene, raising the possibility of identifying individuals genetically predisposed to glaucoma. We collected DNA samples from 426 unselected UK POAG patients and analyzed them for MYOC mutations. The Q368X mutation was found in six patients (1.4%). No other mutations were identified, suggesting that amongst patients unselected for family history, the prevalence of MYOC mutations in the UK is lower than in other populations. Genetic and glaucoma screening was offered to first-degree relatives of these six probands (group 1) and of age/sex-matched mutation-negative controls (group 2). Of 11 group-1 relatives, three carried Q368X, one of whom already had glaucoma. Notably, of the 13 relatives in both groups who were mutation negative, one was already being treated for ocular hypertension. We therefore caution against changing glaucoma surveillance regimens in such individuals and suggest that routine untargeted genetic testing for MYOC mutations in patients with POAG would be of limited value until additional significant genetic risk factors are identified.
authors.affiliation: Division of Medical Genetics, Adrian Building, University of Leicester, University Road, LE1 7RH, Leicester, UK. maldred@hgmp.mrc.ac.uk
authors.forename: Micheala A
authors.initials: MA
authors.lastname: Aldred
authors.forename: Laura
authors.initials: L
authors.lastname: Baumber
authors.forename: Alison
authors.initials: A
authors.lastname: Hill
authors.forename: Edward C
authors.initials: EC
authors.lastname: Schwalbe
authors.forename: Kai
authors.initials: K
authors.lastname: Goh
authors.forename: Wojciech
authors.initials: W
authors.lastname: Karwatowski
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D006113:United Kingdom / Q000453:epidemiology; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin