title: Myocilin analysis by DHPLC in French POAG patients: increased prevalence of Q368X mutation.
abstract: Primary open-angle glaucoma (POAG) is a prevalent optic neuropathy with complex genetics. A small number of patients carry a mutation in the coding region of the myocilin (MYOC) gene. The nature and the frequency of these mutations, however, vary substantially, notably with the age at onset and the ethnic origin of the patients. Here, we showed that denaturing high performance liquid chromatography (DHPLC) is an appropriate method for screening carriers of MYOC mutations. We have applied the method to a group of 237 POAG patients and 108 control subjects from France. Mutations were found in 17 (7.5%) patients and in none of the controls. A single mutation, Q368X (c.1102C>T), accounted for the majority (12/17) of these mutations, corresponding to a frequency of 5% among POAG patients, the highest ever reported for this mutation. Furthermore, analysis of allelic associations at closely linked microsatellite markers indicated that most, if not all, patients inherited Q368X from a same ancestor. Five other patients carried four distinct mutations, including N480K (c.1440C>A) (2 cases), I499F (c.1495A>T), G367R (c.1099G>A) and T438I (c.1313C>T), which is reported here for the first time. Altogether, MYOC mutations in French patients were associated with a significantly increased intraocular pressure at diagnosis. In addition, the age at diagnosis of patients with a mutation other than Q368X was significantly younger than that of Q368X carriers or of patients with a normal MYOC. Based on these observations, a screening strategy of MYOC mutations in French POAG patients is briefly outlined.
authors.affiliation: INSERM U580, Hôpital Necker, Paris, France.
authors.forename: Rahma
authors.initials: R
authors.lastname: Melki
authors.forename: Ahmed
authors.initials: A
authors.lastname: Belmouden
authors.forename: Antoine
authors.initials: A
authors.lastname: Brézin
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics*; D005973:Glutamine / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009691:Nucleic Acid Denaturation / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D012189:Retrospective Studies; D014129:Trabecular Meshwork / Q000473:pathology; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D005973:Glutamine; D006023:Glycoproteins; D000099179:Myocilin