Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects
BackgroundPrimary 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 a...
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Frontiers Media S.A.
2025-06-01
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| author | Miao He Wangji Zhou Yixuan Li Qiaoling Chen Yaping Liu Xinlun Tian Xue Zhang |
| author_facet | Miao He Wangji Zhou Yixuan Li Qiaoling Chen Yaping Liu Xinlun Tian Xue Zhang |
| author_sort | Miao He |
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| description | BackgroundPrimary 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.MethodsWe investigated a male patient with suspected PCD who exhibited “9 + 2” ultrastructural abnormalities in both bronchial cilia and sperm flagella. Whole exome sequencing 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.ResultsWhole exome sequencing 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.ConclusionOur 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. |
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| publishDate | 2025-06-01 |
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| spelling | doaj-art-6a98711159694583ba5cd6edbbc0924d2025-08-20T02:20:40ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15746841574684Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defectsMiao He0Wangji Zhou1Yixuan Li2Qiaoling Chen3Yaping Liu4Xinlun Tian5Xue Zhang6McKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaState Key Laboratory for Complex Severe and Rare Diseases, State Key Sci-tech Infrastructure for Translational Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaState Key Laboratory for Complex Severe and Rare Diseases, State Key Sci-tech Infrastructure for Translational Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaMcKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, ChinaBackgroundPrimary 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.MethodsWe investigated a male patient with suspected PCD who exhibited “9 + 2” ultrastructural abnormalities in both bronchial cilia and sperm flagella. Whole exome sequencing 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.ResultsWhole exome sequencing 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fmed.2025.1574684/fullCFAP47variant pathogenicityprimary ciliary dyskinesiaciliagenetic testing |
| spellingShingle | Miao He Wangji Zhou Yixuan Li Qiaoling Chen Yaping Liu Xinlun Tian Xue Zhang Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects Frontiers in Medicine CFAP47 variant pathogenicity primary ciliary dyskinesia cilia genetic testing |
| title | Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects |
| title_full | Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects |
| title_fullStr | Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects |
| title_full_unstemmed | Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects |
| title_short | Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects |
| title_sort | case report identification of a novel hemizygous cfap47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects |
| topic | CFAP47 variant pathogenicity primary ciliary dyskinesia cilia genetic testing |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1574684/full |
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