Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
复制标题
两个不同表型（包括孤立性先天性白内障）家系中新型眼脑肾综合征（OCRL）基因变异的鉴定和功能分析
作者：
A. Shalaby;Peter Emery;D. Baralle;T. Dabir;Shahiba Begum;S. Waller;L. Tabernero;M. Lowe;J. Self
目的检测两例无血缘关系的先天性白内障先证者的遗传变异并进行功能分析。方法对两个家系进行临床检查、表型、分离和功能分析。结果发现一种新的OCRL基因变异体（c.1964A>T，p.（Asp655Val））。这种变体导致OCRL蛋白折叠缺陷和细胞质错误定位。此外，该变体靠近Rab结合位点的位置可能与膜靶向异常有关。结论OCRL基因突变可表现为明显孤立的先天性白内障，提示对先天性白内障进行早期基因诊断的重要性。
Purpose To identify the genetic variation in two unrelated probands with congenital cataract and to perform functional analysis of the detected variants. Methods Clinical examination and phenotyping, segregation, and functional analysis were performed for the two studied pedigrees. Results A novel OCRL gene variant (c.1964A>T, p. (Asp655Val)) was identified. This variant causes defects in OCRL protein folding and mislocalization to the cytoplasm. In addition, the variant’s location close to the Rab binding site is likely to be associated with membrane targeting abnormalities. Conclusions The results highlight the importance of early genetic diagnosis in infants with congenital cataract and show that mutations in the OCRL gene can present as apparently isolated congenital cataract.