Mutations in CFAP47, a previously reported MMAF causative gene, also contribute to the respiratory defects in patients with PCD

Abstract

AbstractBackgroundPrimary ciliary dyskinesia (PCD) is a genetic ciliopathy characterized by dysfunction of motile cilia. Currently, approximately 50 causative genes accounting for 60%–70% of all PCD cases have been identified in PCD‐affected individuals, but the etiology in approximately 30%–40% of PCD cases remains unknown.MethodsWe analyzed the clinical and genetic data of two PCD individuals who were suspected of having PCD. Whole‐exome sequencing and Sanger sequencing were performed to identify and verify the variants in CFAP47. We also evaluated the expression of CFAP47 by real‐time quantitative PCR and immunofluorescence. Transmission electron microscopy in respiratory epithelial cells was also conducted to analyze ciliary function.ResultsTwo hemizygous missense variants of X‐linked CFAP47 in two unrelated PCD individuals were identified. The expression of CFAP47 in two PCD individuals was significantly reduced in vivo and in vitro assays. A reduction in the amount of epithelial ciliary cells and basal bodies from PCD individuals was also observed.ConclusionsWe describe two hemizygous missense variants of X‐linked CFAP47 in two unrelated PCD individuals and prove CFAP47 variants are related to a reduced number of epithelial ciliary cells. Therefore, we suggest that CFAP47 should be known as a novel pathogenic gene of human PCD.