RESUMO
PURPOSE: To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families. METHODS: This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negative or heterozygous probands. Then the coding exons of MYOC were sequenced in patients who had no mutation in CYP1B1 or carried heterozygous CYP1B1 mutation. RESULTS: Twelve CYP1B1 mutations were identified in 43 PCG pedigrees. Three of them were novel (p.R163C, p.C470Y, and g.4330-4331delTG) and associated with moderate to severe phenotypes. Two novel intronic polymorphisms in CYP1B1 were identified in addition to those previously described. The g.4339delG was the most frequent mutation detected in 31 families (34.44%), followed by the p.G61E in seven families (7.77%). The remaining mutations (p.R163C, p.E173K, g.4330-4331delTG, p.E229K, p.R390S, p.R368H, p.R469W, p.C470Y, and g.7901-7913del13bp) were infrequent. One family with the p.R390S mutation showed both PCG and primary open angle glaucoma (POAG) phenotypes. One proband was heterozygous for p.T193K mutation in MYOC. This mutation has been initially associated with POAG, but never with PCG. CONCLUSIONS: Our results support that mutations in CYP1B1 are a major cause for PCG in the Moroccan population with a predominance of the g.4339delG mutation. Furthermore, these results demonstrate the diversity of CYP1B1 mutations, while suggesting a modest role of MYOC in Moroccan PCG.
