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

Abstract

BackgroundPrimary ciliary dyskinesia (PCD) is an autosomal recessive disorder. The genetic factors contributing to PCD pathogenesis remain elusive for approximately 20-35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of sporadic PCD genes using whole-exome sequencing (WES). ResultAll patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy (TEM) images of cilia. WES and bioinformatic analysis were then conducted for patients with PCD. Identi ed 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, 15 rare variants were identi ed in ve patients with PCD. Five new variants of CCDC40, DNAH1, DNAAF3, and DNAI1 were considered causative variants and included one splicing and three homozygous variants. ConclusionOur study demonstrated that patients with PCD carry rare causative variants of multiple genes. Our ndings indicated that not only known causative genes but also other functional genes should be considered for heterogeneous genetic disorders.