Clinical and genetic analysis of patients with primary ciliary dyskinesia caused by novel DNAAF3 mutations

Primary ciliary dyskinesia (PCD) is a rare phenotypically and genetically heterogeneous disorder resulting from abnormal cilia ultrastructure and function. Few studies have reported the phenotype and genetic characteristics of PCD caused by mutations in DNAAF3 . In this study, four PCD patients with DNAAF3 mutations underwent extensive clinical assessments, cilia ultrastructural and motion evaluations. All patients presented with situs inversus totalis, neonatal respiratory distress, and sinusitis; however, they did not have recurrent infections of the lower airways. The nasal nitric oxide level of these patients was markedly reduced. The respiratory cilia were found to be uniformly immotile, with their dynein arms defects. A total of 7 (5 novel) variants in DNAAF3 were identified and cosegregated in their families by Trio-based whole-exome sequencing. As the first report on DNAAF3 mutations in PCD patients in China, our study not only contributes to a deeper appreciation of the phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis of and counseling for PCD.