两个具有不同表型（包括孤立性先天性白内障）的家系中一种新型 Lowe 眼脑肾综合征（OCRL）基因变异的鉴定与功能分析
Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe () gene variant in two pedigrees with varying phenotypes including isolated congenital cataract.
作者信息
Shalaby Ahmed K, Emery-Billcliff Peter, Baralle Diana, Dabir Tabib, Begum Shahiba, Waller Sarah, Tabernero Lydia, Lowe Martin, Self James
机构信息
Ophthalmology Department, Princess of Wales Hospital, Manchester, UK.
School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
出版信息
Mol Vis. 2018 Dec 31;24:847-852. eCollection 2018.
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 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 gene can present as apparently isolated congenital cataract.
目的
鉴定两名先天性白内障无关先证者的基因变异，并对检测到的变异进行功能分析。
方法
对两个研究家系进行临床检查、表型分析、分离分析和功能分析。
结果
鉴定出一种新的基因变异（c.1964A>T，p.（Asp655Val））。该变异导致OCRL蛋白折叠缺陷并错误定位于细胞质。此外，该变异靠近Rab结合位点的位置可能与膜靶向异常有关。
结论
结果突出了先天性白内障婴儿早期基因诊断的重要性，并表明该基因的突变可表现为明显孤立的先天性白内障。
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