Genotype-phenotype correlation in Moroccan patients with primary congenital glaucoma.

PURPOSE: To investigate the genotype-phenotype correlation in a large cohort of Moroccan primary congenital glaucoma (PCG) in which CYP1B1 mutation spectrum was recently reported by our group. METHODS: This study included 94 patients from 84 unrelated Moroccan PCG families with or without CYP1B1 mutations. Clinical features, severity of the phenotype, and prognosis were mainly compared in patients with no CYP1B1 mutations, double CYP1B1 null alleles or nondouble null but other CYP1B1 mutations; most of them were hypomorphic mutations. Statistical analyses were performed using SAS and SPSS softwares. Significance was set at P<0.05. RESULTS: Mean of intraocular pressure, corneal diameter and number of surgery values and cup-to-disc ratios, and percentages of patients with bilateral PCG, eyes with severe opacities and severe phenotype, and those that needed >1 trabeculectomy were significantly higher in the CYP1B1 mutation carriers (n=51) than in the no CYP1B1 mutation group (n=43). The same results were observed when patients with double CYP1B1 null alleles (n=34) were compared with those with no CYP1B1 mutation. The comparison between the no CYP1B1 mutation patients and those with nondouble null but other CYP1B1 mutations (n=17) showed significant differences in the percentage of bilateral PCG and percentages of eyes with severe opacities and severe phenotype. When the double CYP1B1 null allele carriers were compared with the nondouble null but other CYP1B1 mutation group, only significant differences were observed in the mean number of surgery values. Multivariate analysis revealed that, after adjustment of the parameters that showed significant differences in univariate analyses, corneal diameter was the main factor explaining the severity of PCG only in the double CYP1B1 null allele carriers. CONCLUSIONS: This is the first report of genotype-phenotype correlation in a large cohort of Moroccan PCG. Our results revealed that the worst phenotype and prognosis were observed in the double null CYP1B1 allele carriers followed by the nondouble null but other CYP1B1 mutations. This will contribute to the prediction of the prognosis of the disease.

Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: three novel mutations in CYP1B1.

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.