Wang Xun, Qin Yanli, Abudoukeremuahong Aierxiding, Dongye Meimei, Zhang Xulin, Wang Dongni, Li Jing, Lin Zhuoling, Yang Yahan, Ding Lin, Lin Haotian
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Ophthalmology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Ann Transl Med. 2021 Feb;9(3):235. doi: 10.21037/atm-20-4275.
Congenital cataract (CC) is a congenital abnormality characterized by lens opacity present at birth and is associated with highly heterogeneous clinical manifestations. Lens-specific integral membrane protein () gene expression is localized to tight junctional domains of different lens fiber membranes. To date, only four mutations in have been reported to be associated with congenital or presenile cataracts. Due to the rarity of variants detected in the gene, there is limited progress in understanding the correlation between the genotype and phenotype of patients with mutations in .
A total of four Chinese families with CCs were recruited for this study, including three families inheriting in an autosomal dominant (AD) pattern and one sporadic case. Genomic DNA was extracted from the leukocytes of peripheral blood collected from all available patients. Whole-exome sequencing (WES) was performed on all probands and at least one of their parents. Bioinformatics analysis was performed to evaluate the pathogenicity of the candidate variants. Exon 4 of was amplified by polymerase chain reaction and directly sequenced. All patients underwent full ocular examinations. This was an observational study to explore the genotype-phenotype relationships in the four families with a common candidate variant.
Various ocular phenotypes were detected in these families, mainly including CCs, elongated axial length, and myopia-related fundus changes. The gene mutation, p.Arg130Cys, was detected in all patients. This was further confirmed by Sanger sequencing. The proportion of probands with this mutation in our CCs database was 3.1% (4/130), which indicated that this mutation appears to be a frequent cause of cataracts in the Han Chinese population. This variation has been reported by other investigators before and was correlated with isolated cataracts.
This is the first study that reports various ocular phenotypes associated with the p.Arg130Cys mutation in the gene, which indicated the phenotypic heterogeneity of this gene. might not only function as an integral membrane protein in lens fiber cells but also be associated with the axial development of the eyeball. Functional studies of the gene are important and should receive more attention.
先天性白内障（CC）是一种先天性异常，其特征为出生时晶状体混浊，且伴有高度异质性的临床表现。晶状体特异性整合膜蛋白（）基因表达定位于不同晶状体纤维膜的紧密连接结构域。迄今为止，仅报道了该基因中的四个突变与先天性或早老性白内障相关。由于在该基因中检测到的变异罕见，对于该基因突变患者的基因型与表型之间的相关性了解进展有限。
本研究共招募了四个患有先天性白内障的中国家庭，包括三个以常染色体显性（AD）模式遗传的家庭和一个散发病例。从所有可用患者外周血白细胞中提取基因组DNA。对所有先证者及其至少一位父母进行全外显子组测序（WES）。进行生物信息学分析以评估候选变异的致病性。通过聚合酶链反应扩增该基因的第4外显子并直接测序。所有患者均接受了全面的眼部检查。这是一项观察性研究，旨在探索四个具有共同候选变异的家庭中的基因型-表型关系。
在这些家庭中检测到了各种眼部表型，主要包括先天性白内障、眼轴长度延长以及与近视相关的眼底改变。在所有患者中均检测到该基因突变，即p.Arg130Cys。这通过桑格测序进一步得到证实。在我们的先天性白内障数据库中，携带此突变的先证者比例为3.1%（4/130）），这表明该突变似乎是汉族人群白内障的常见病因。此前其他研究者已报道过这种变异，且其与单纯性白内障相关。
这是第一项报道与该基因p.Arg130Cys突变相关的各种眼部表型的研究，这表明该基因的表型异质性。该基因可能不仅在晶状体纤维细胞中作为整合膜蛋白发挥作用，还与眼球的轴向发育有关。对该基因的功能研究很重要，应受到更多关注。
