中国先天性白内障患者的基因突变谱。

Mutational spectrum in a Chinese cohort with congenital cataracts.

机构信息

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China.

Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China.

出版信息

Mol Genet Genomic Med. 2023 Sep;11(9):e2196. doi: 10.1002/mgg3.2196. Epub 2023 Jun 20.

DOI:10.1002/mgg3.2196

PMID:37337769

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10496047/

Abstract

BACKGROUND

To identify the mutational spectrum in a Chinese cohort with congenital cataracts.

METHODS

Probands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel-based next-generation sequencing, then classified into a cohort for further mutational analysis.

RESULTS

After recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of congenital cataracts, and 56.88% (124/218) of patients received a molecular diagnosis. Eighty-four distinct variants distributed among 43 different genes, including 42 previously reported variants and 42 novel variants, were detected, and 49 gene variants were causally associated with patient phenotypes; 27.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD, and the three genes covered 33.06% of cases (41/124) with molecular diagnosis. The majority of genes were classified as genes involved in nonsyndromic congenital cataracts (19/43, 44.19%) and were responsible for 56.45% of cases (70/124). The majority of functional and nucleotide changes were missense variants (53/84, 63.10%) and substitution variants (74/84, 88.10%), respectively. Nine de novo variants were identified.

CONCLUSION

This study provides a reference for individualized genetic counseling and further extends the mutational spectrum of congenital cataracts.

摘要

背景

鉴定一个中国先天性白内障患者队列的突变谱。

方法

招募了 164 名患有先天性白内障的先证者及其受影响或未受影响的可利用的家庭成员进行临床检查和基于面板的下一代测序，然后将其分为队列进行进一步的突变分析。

结果

在招募后（n=442；228 名男性和 214 名女性），49.32%（218/442）的受试者被临床诊断为先天性白内障，56.88%（124/218）的患者接受了分子诊断。共检测到 84 个不同的变异分布在 43 个不同的基因中，包括 42 个先前报道的变异和 42 个新的变异，其中 49 个基因变异与患者表型有关；42 个变异（23/84）常见于 PAX6、GJA8 和 CRYGD 中，这三个基因覆盖了 33.06%（41/124）具有分子诊断的病例。大多数基因被归类为非综合征先天性白内障相关基因（19/43，44.19%），占 124 例分子诊断病例的 56.45%（70/124）。大多数功能和核苷酸变化分别为错义变异（53/84，63.10%）和替换变异（74/84，88.10%）。共鉴定出 9 个新生变异。