一种与先天性后囊下白内障相关的 PITX3 基因 OAR 结构域的新型突变。
A novel mutation in the OAR domain of PITX3 associated with congenital posterior subcapsular cataract.
机构信息
Department of Ophthalmology and the Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, 83 Fenyang Rd, Shanghai, People's Republic of China.
The Key Laboratory of Myopia, Ministry of Health, 83 Fenyang Rd, Shanghai, People's Republic of China.
出版信息
BMC Med Genet. 2019 Mar 20;20(1):42. doi: 10.1186/s12881-019-0782-2.
BACKGROUND
Congenital cataract is the most common cause of blindness among children worldwide. The aim of this study was to identify causative mutations in a Chinese family with isolated autosomal dominant posterior subcapsular cataract.
METHODS
The proband and her parents underwent full ophthalmological examinations. DNA was extracted from the participants' peripheral venous blood. The mutation was identified via panel-based next-generation sequencing (NGS) and was validated via Sanger sequencing.
RESULTS
Posterior subcapsular lenticular opacity was observed in both of the proband's eyes. The novel deletion mutation c.797_814del, p.Ser266_Ala271del in the PITX3 gene was identified in the proband and her father. This mutation is located within the otp/aristaless/rax (OAR) domain at the COOH-terminus of the protein, which functions in DNA binding and transactivation. This mutation would result in a deletion of 6 amino acid residues at the C terminal of the protein.
CONCLUSIONS
The mutation c.797_814del, p.Ser266_Ala271del is a novel mutation in the conserved DNA-binding OAR domain of PITX3 that causes congenital cataract.
背景
先天性白内障是全球儿童失明的最常见原因。本研究旨在鉴定一个常染色体显性遗传的后囊下白内障家系的致病突变。
方法
先证者及其父母接受了全面的眼科检查。从参与者的外周静脉血中提取 DNA。通过基于面板的下一代测序（NGS）鉴定突变，并通过 Sanger 测序进行验证。
结果
先证者双眼均出现后囊下晶状体混浊。在先证者及其父亲中发现了 PITX3 基因的新型缺失突变 c.797_814del，p.Ser266_Ala271del。该突变位于蛋白 COOH 端的 otp/aristaless/rax（OAR）结构域内，该结构域在 DNA 结合和转录激活中起作用。该突变将导致蛋白 C 末端缺失 6 个氨基酸残基。
结论
突变 c.797_814del，p.Ser266_Ala271del 是 PITX3 保守 DNA 结合 OAR 结构域中的一个新突变，导致先天性白内障。
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