中国家族性或散发性小儿白内障患者的临床和遗传特征。

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract.

机构信息

The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.

出版信息

Orphanet J Rare Dis. 2018 Jun 18;13(1):94. doi: 10.1186/s13023-018-0828-0.

BACKGROUND

Pediatric cataract is a clinically and genetically heterogeneous disease which is a significant cause of lifelong visual impairment and treatable blindness. Our study aims to investigate the genotype spectrum in a group of Chinese patients with pediatric cataract.

METHODS

We enrolled 39 families with pediatric cataract from October 2015 to April 2016. DNA samples of the probands were analyzed by target next-generation sequencing. Variants were validated using Sanger sequencing in the probands and available family members.

RESULTS

In our cohort of 39 cases with different types of pediatric cataract, 23 cases were found to harbor putative pathogenic variants in 15 genes: CRYAA, CRYBA1, CRYBA4, CRYBB1, CRYGC, CRYGD, MIP, GCNT2, IARS2, NHS, BCOR, BFSP2, FYCO1, MAF, and PAX6. The mutation detection rates in the familial and sporadic cases were 75 and 47.8%, respectively. Of the 23 causative variants, over half were novel.

CONCLUSIONS

This is a rare report of systematic mutation screening analysis of pediatric cataract in a comparably large cohort of Chinese patients. Our observations enrich the mutation spectrum of pediatric cataract. Next-generation sequencing provides significant diagnostic information for pediatric cataract cases, especially when considering sporadic and subtle syndromal cases.

背景

小儿白内障是一种临床表现和遗传学上均具有异质性的疾病，是导致儿童终身视力损害和可治疗性盲的重要原因。我们的研究旨在调查一组中国小儿白内障患者的基因型谱。

方法

我们招募了 2015 年 10 月至 2016 年 4 月期间的 39 个小儿白内障家系。对先证者的 DNA 样本进行靶向下一代测序分析。通过先证者及其可利用的家庭成员的 Sanger 测序对变异进行验证。

结果

在我们的 39 例不同类型小儿白内障患者队列中，发现 15 个基因中有 23 个家系存在潜在的致病性变异：CRYAA、CRYBA1、CRYBA4、CRYBB1、CRYGC、CRYGD、MIP、GCNT2、IARS2、NHS、BCOR、BFSP2、FYCO1、MAF 和 PAX6。家族性和散发性病例的突变检出率分别为 75%和 47.8%。在 23 个致病变异中，超过一半是新的。