Pathogenic variants identified using whole‐exome sequencing in Chinese patients with primary ciliary dyskinesia
The genetic factors contributing to primary ciliary dyskinesia (PCD), a rare autosomal recessive disorder, remain elusive for ~20%–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of PCD‐associated pathogenic candidate genes using whole‐ex...
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Published in | American journal of medical genetics. Part A Vol. 188; no. 10; pp. 3024 - 3031 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.10.2022
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | The genetic factors contributing to primary ciliary dyskinesia (PCD), a rare autosomal recessive disorder, remain elusive for ~20%–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of PCD‐associated pathogenic candidate genes using whole‐exome sequencing (WES). All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy images of cilia. WES and bioinformatic analysis were then conducted on patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 13 rare variants were identified in patients with PCD, among which were three homozygous causative variants (including one splicing variant) in the PCD‐associated genes CCDC40 and DNAI1. Moreover, two stop‐gain heterozygous variants of DNAAF3 and DNAH1 were classified as pathogenic variants based on the ACMG criteria. This study identified novel potential pathogenic genetic factors associated with PCD. Noteworthy, the patients with PCD carried multiple rare causative gene variants, thereby suggesting that known causative genes along with other functional genes should be considered for such heterogeneous genetic disorders. |
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Bibliography: | Funding information Yutian Ye, Qijun Huang, and Lipeng Chen contributed equally to this study. Guangdong Provincial Science and Technology Project, Grant/Award Numbers: 2018A030310674, 2021A1515012325; Key Laboratory of Shenzhen Respiratory Diseases, Grant/Award Number: ZDSYS201504301616234; Natural Science Foundation of Guangdong Province, Grant/Award Number: 2017A020214016; Shenzhen Science and Technology Project, Grant/Award Number: JCYJ20170413093032806 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1552-4825 1552-4833 |
DOI: | 10.1002/ajmg.a.62912 |