Taylan Sekeroglu Hande, Karaosmanoglu Beren, Taskiran Ekim Z, Simsek Kiper Pelin O, Alikasifoglu Mehmet, Boduroglu Koray, Coskun Turgay, Utine Gulen Eda
Department of Ophthalmology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Department of Medical Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Mol Syndromol. 2020 Dec;11(5-6):302-308. doi: 10.1159/000510481. Epub 2020 Sep 9.
Congenital cataract, which refers to lenticular opacity diagnosed at birth or more commonly during the first year of life, is one of the leading causes of childhood blindness. Molecular understanding of the disease pathogenesis has evolved thanks to many studies based on modern technologies. In this study, we aimed to identify and discuss the molecular etiology of nonsyndromic or nonmetabolic bilateral congenital cataract by whole-exome sequencing (WES). Patients with bilateral congenital cataract presumed to be isolated after metabolic and genetic evaluation were enrolled in the study. All patients underwent detailed ophthalmological examination and bilateral cataract surgery. DNA samples of the probands, parents, and available affected family members were analyzed by WES. Variants were validated and confirmed by Sanger sequencing in all probands and in available affected family members. A total of 4 patients (3 girls and 1 boy) were recruited. Two patients had nuclear, 1 patient had total, and 1 patient had combined lamellar and sutural cataract. One family had consanguinity. A heterozygous c.215+1G>A mutation in , heterozygous c.432C>G (p.Tyr144Ter) mutation in , heterozygous c.70A>C (p.Pro24Thr) mutation in , and a heterozygous c.466G>A (p.Gly156Arg) mutation in were detected. All these mutations were confirmed by Sanger sequencing in selected affected individuals. The current study identified all causative mutations of congenital cataract in the crystalline genes. The results confirmed that WES is a very useful tool in the investigation of the diseases with heterogeneous genetic background.
先天性白内障是指在出生时或更常见于出生后第一年被诊断出的晶状体混浊，是儿童失明的主要原因之一。由于许多基于现代技术的研究，对该疾病发病机制的分子理解有了进展。在本研究中，我们旨在通过全外显子组测序（WES）来识别和讨论非综合征性或非代谢性双侧先天性白内障的分子病因。代谢和基因评估后被认为是孤立性双侧先天性白内障的患者被纳入研究。所有患者均接受了详细的眼科检查和双侧白内障手术。先证者、父母及可用的患病家庭成员的DNA样本通过WES进行分析。所有先证者及可用的患病家庭成员的变异通过桑格测序进行验证和确认。共招募了4名患者（3名女孩和1名男孩）。2名患者患有核性白内障，1名患者患有完全性白内障，1名患者患有板层和缝性白内障合并症。一个家族存在近亲结婚情况。检测到 中存在杂合的c.215+1G>A突变、 中存在杂合的c.432C>G（p.Tyr144Ter）突变、 中存在杂合的c.70A>C（p.Pro24Thr）突变以及 中存在杂合的c.466G>A（p.Gly156Arg）突变。所有这些突变在选定的患病个体中通过桑格测序得到了确认。本研究确定了晶状体基因中先天性白内障的所有致病突变。结果证实，WES是研究具有异质性遗传背景疾病的非常有用的工具。
