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新一代测序揭示中国瓦登伯革氏综合征患者的高度遗传异质性

High Genetic Heterogeneity in Chinese Patients With Waardenburg Syndrome Revealed by Next-Generation Sequencing.

作者信息

Zhang Sen, Xu Hongen, Tian Yongan, Liu Danhua, Hou Xinyue, Zeng Beiping, Chen Bei, Liu Huanfei, Li Ruijun, Li Xiaohua, Zuo Bin, Tang Ryan, Tang Wenxue

机构信息

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Precision Medicine Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, China.

出版信息

Front Genet. 2021 Jun 4;12:643546. doi: 10.3389/fgene.2021.643546. eCollection 2021.

DOI:10.3389/fgene.2021.643546
PMID:34149797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8212959/
Abstract

OBJECTIVE

This study aimed to explore the genetic causes of probands who were diagnosed with Waardenburg syndrome (WS) or congenital sensorineural hearing loss.

METHODS

A detailed physical and audiological examinations were carried out to make an accurate diagnosis of 14 patients from seven unrelated families. We performed whole-exome sequencing in probands to detect the potential genetic causes and further validated them by Sanger sequencing in the probands and their family members.

RESULTS

The genetic causes for all 14 patients with WS or congenital sensorineural hearing loss were identified. A total of seven heterozygous variants including c.1459C > T, c.123del, and c.959-409_1173+3402del of gene (NM_181459.4), c.198_262del and c.529_556del of gene (NM_006941.4), and c.731G > A and c.970dup of gene (NM_000248.3) were found for the first time. Of these mutations, we had confirmed two (c.1459C > T and c.970dup) are by Sanger sequencing of variants in the probands and their parents.

CONCLUSION

We revealed a total of seven novel mutations in , , and , which underlie the pathogenesis of WS. The clinical and genetic characterization of these families with WS elucidated high heterogeneity in Chinese patients with WS. This study expands the database of , , and mutations and improves our understanding of the causes of WS.

摘要

目的

本研究旨在探究被诊断为瓦登伯革氏综合征（WS）或先天性感音神经性听力损失的先证者的遗传病因。

方法

对来自七个无关家庭的14名患者进行了详细的体格检查和听力学检查，以做出准确诊断。我们在先证者中进行了全外显子组测序，以检测潜在的遗传病因，并通过对先证者及其家庭成员进行桑格测序进一步验证。

结果

确定了所有14例WS或先天性感音神经性听力损失患者的遗传病因。首次发现了总共七个杂合变异，包括基因（NM_181459.4）的c.1459C>T、c.123del和c.959-409_1173+3402del，基因（NM_006941.4）的c.198_262del和c.529_556del，以及基因（NM_000248.3）的c.731G>A和c.970dup。在这些突变中，我们通过对先证者及其父母的变异进行桑格测序，确认了两个（c.1459C>T和c.970dup）。

结论

我们在、和中总共发现了七个新突变，这些突变是WS发病机制的基础。这些WS家庭的临床和遗传特征阐明了中国WS患者的高度异质性。本研究扩展了、和的突变数据库，提高了我们对WS病因的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/3ab759c0d1b5/fgene-12-643546-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/96eeb47aa67b/fgene-12-643546-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/a3caf75cf387/fgene-12-643546-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/3ab759c0d1b5/fgene-12-643546-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/96eeb47aa67b/fgene-12-643546-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/a3caf75cf387/fgene-12-643546-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d70b/8212959/3ab759c0d1b5/fgene-12-643546-g003.jpg

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Perrault syndrome: Clinical report and retrospective analysis.佩罗特综合征：临床报告及回顾性分析。
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通过下一代测序技术在 PAX3、SOX10、EDNRB 和 MITF 基因中鉴定出 9 种新型变异与 Waardenburg 综合征相关。
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