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
- 1McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
- 2Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- 3The State Key Laboratory for Complex Severe and Rare Diseases, Center for Rare Diseases, Peking Union Medical College Hospital, Beijing, China
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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 He, Zhou, Li, Chen, Liu, Tian and Zhang. 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.
* Correspondence:
Yaping Liu, The State Key Laboratory for Complex Severe and Rare Diseases, Center for Rare Diseases, Peking Union Medical College Hospital, Beijing, China
Xinlun Tian, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
Xue Zhang, McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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