Berraho Amina, Serrou Aziza, Fritez Nabila, El Annas Abdessamad, Bencherifa Fatiha, Gaboun Fatima, Hilal Latifa
*Service d'Ophtalmologie B, Hôpital des Spécialités, CHU Ibn Sina, Equipe de Recherche sur les Maladies Oculaires, Faculté des Médecine et de Pharmacie †Laboratoire de Biologie Générale et Zoologie-Equipe de Biologie des Organismes et des Populations, Université Mohammed V-Agdal, Faculté des Sciences ‡Institut National de la Recherche Agronomique, UR Biotechnologie, Rabat, Morocco.
J Glaucoma. 2015 Apr-May;24(4):297-305. doi: 10.1097/IJG.0b013e31829f99b7.
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.
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.
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.
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.
在我们小组最近报道了CYP1B1突变谱的一大群摩洛哥原发性先天性青光眼（PCG）患者中，研究基因型与表型的相关性。
本研究纳入了来自84个不相关的摩洛哥PCG家庭的94例患者，这些患者有或没有CYP1B1突变。主要比较了无CYP1B1突变、CYP1B1双无效等位基因或非双无效但有其他CYP1B1突变（大多数为亚型突变）的患者的临床特征、表型严重程度和预后。使用SAS和SPSS软件进行统计分析。显著性设定为P<0.05。
CYP1B1突变携带者（n=51）的眼压平均值、角膜直径、手术次数和杯盘比，以及双侧PCG患者、严重混浊眼和严重表型患者的百分比，以及需要进行>1次小梁切除术的患者百分比，均显著高于无CYP1B1突变组（n=43）。将CYP1B1双无效等位基因患者（n=34）与无CYP1B1突变患者进行比较时，观察到相同的结果。无CYP1B1突变患者与非双无效但有其他CYP1B1突变患者（n=17）之间的比较显示，双侧PCG百分比以及严重混浊眼和严重表型眼的百分比存在显著差异。当将CYP1B1双无效等位基因携带者与非双无效但有其他CYP1B1突变组进行比较时，仅在手术次数平均值上观察到显著差异。多变量分析显示，在对单变量分析中显示出显著差异的参数进行调整后，角膜直径是仅在CYP1B1双无效等位基因携带者中解释PCG严重程度的主要因素。
这是关于一大群摩洛哥PCG患者基因型与表型相关性的首次报告。我们的结果显示，在CYP1B1双无效等位基因携带者中观察到最差的表型和预后，其次是非双无效但有其他CYP1B1突变的患者。这将有助于预测该疾病的预后。
