Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia

Ye, Yutian1; Huang, Qijun1; Chen, Lipeng2; Yuan, Fang1; Liu, Shengguo1; Zhang, Xiangxia1; Chen, Rongchang1,3; Fu, Yingyun1; Yue, Yongjian1

2022-07-01

10.1002/ajmg.a.62912

AMERICAN JOURNAL OF MEDICAL GENETICS PART A   Impact Factor & Quartile

1552-4825

1552-4833

The genetic factors contributing to primary ciliary dyskinesia (PCD), a rare autosomal recessive disorder, remain elusive for similar to 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.

DNAAF3 DNAI1 pathogenic primary ciliary dyskinesia whole-exome sequencing

SCI

English

First ; Corresponding

Guangdong Provincial Science and Technology Project["2018A030310674","2021A1515012325"] ; Key Laboratory of Shenzhen Respiratory Diseases[ZDSYS201504301616234] ; Natural Science Foundation of Guangdong Province[2017A020214016] ; Shenzhen Science and Technology Project[JCYJ20170413093032806]

Genetics & Heredity

Genetics & Heredity

WOS:000829050600001

WILEY

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Jinan Univ, Clin Med Coll 2, Shenzhen Inst Resp Dis,Affiliated Hosp 1, Southern Univ Sci & Technol,Shenzhen Peoples Hosp, Shenzhen, Guangdong, Peoples R China
2.Jinan Univ, Clin Med Coll 2, Clin Ctr, Shenzhen Peoples Hosp, Shenzhen, Guangdong, Peoples R China
3.Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Respirat Dis, Guangzhou, Guangdong, Peoples R China

Ye, Yutian,Huang, Qijun,Chen, Lipeng,et al. Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A,2022.

Ye, Yutian.,Huang, Qijun.,Chen, Lipeng.,Yuan, Fang.,Liu, Shengguo.,...&Yue, Yongjian.(2022).Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia.AMERICAN JOURNAL OF MEDICAL GENETICS PART A.

Ye, Yutian,et al."Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia".AMERICAN JOURNAL OF MEDICAL GENETICS PART A (2022).