Your new experience awaits. Try the new design now and help us make it even better

CASE REPORT article

Front. Med.

Sec. Pulmonary Medicine

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1574684

Identification of a novel hemizygous CFAP47 variant in primary ciliary dyskinesia with dual ciliary and flagellar defects

Provisionally accepted

The final, formatted version of the article will be published soon.

Background: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous ciliopathy caused by structural and functional abnormalities of motile cilia. Although over 50 PCD-associated genes have been reported, the genetic spectrum remains incomplete. CFAP47, a gene linked to multiple morphological abnormalities of the flagella, has recently been implicated in PCD; however, further case studies are needed to strengthen this conclusion.Methods: We investigated a male patient with suspected PCD who exhibited "9+2" ultrastructural abnormalities in both bronchial cilia and sperm flagella. Whole exome sequencing (WES) was performed to screen for pathogenic variants. The candidate variant was analyzed through bioinformatics tools, and CFAP47 expression levels were quantified via qPCR in both patient-derived sperm and an in vitro expression plasmid model.Results: WES identified a hemizygous missense variant, CFAP47 (NM_001304548.2): c.3599T>A (p.Phe1200Tyr) in the patient. The pathogenicity of this variant was assessed through multiple in silico tools, with divergent predictions. Experimental validation revealed significantly decreased CFAP47 mRNA levels in the patient's sperm and the HEK293 cells transfected with mutant plasmid compared to controls, suggesting impaired transcript stability.Conclusion: Our study proposes a novel CFAP47 variant as a likely contributor to PCD, given its impact on mRNA expression. These findings strengthen the association between CFAP47 and PCD pathogenesis and expand the mutation spectrum of this emerging disease gene.

Keywords: CFAP47, variant pathogenicity, primary ciliary dyskinesia, Cilia, Genetic Testing

Received: 18 Feb 2025; Accepted: 02 Jun 2025.

Copyright: © 2025 . This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.