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Abstract #11526 Published in IGR 6-3
CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma
Melki R; Colomb E; Lefort N; Brezin AP; Garchon H-JJournal of Medical Genetics 2004; 41: 647-651
INTRODUCTION: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for < 5% of all POAG cases. The CYP1B1 gene, a member of the cytochrome P450 gene family, is a major cause of primary congenital glaucoma (PCG), a rare and severely blinding disease with recessive inheritance. However, CYP1B1 mutations have also been associated with cases of juvenile-onset glaucoma in some PCG families or shown to modify the age of onset of glaucoma linked to a MYOC mutation in a large family. OBJECTIVE: To investigate the role of CYP1B1 mutations in POAG predisposition, irrespective of the presence of a MYOC mutation. METHODS AND SUBJECTS: CYP1B1 coding region variation was characterised by denaturing high performance liquid chromatography (DHPLC) and sequencing in 236 unrelated French Caucasian POAG patients and 47 population-matched controls. RESULTS: Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and no MYOC mutation. They showed juvenile or middle-age onset of disease (median age at diagnosis, 40 years, range 13-52), significantly earlier than in non-carrier patients. Apart from one, all mutations detected in POAG patients were previously associated with PCG. CONCLUSION: CYP1B1 mutations might pose a significant risk for early-onset POAG and might also modify glaucoma phenotype in patients who do not carry a MYOC mutation.
Dr. H.-J. Garchon, INSERM U580, Hopital Necker, 161 rue de Sevres, 75743 Paris, Cedex 15, France
Classification:
3.4.1 Linkage studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
