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Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of motile cilia. A single patient developed PCD-like recurrent pneumonia, sinusitis, and otitis media seven years after hematopoietic cell transplantation; WES identified a heterozygous CFAP43 nonsense variant, c.4506G>A (p.Trp1502Ter), which may have contributed to Primary Ciliary Dyskinesia features (PMID:39572557). No additional unrelated probands or segregation data support CFAP43 involvement in PCD. Functional studies in sperm flagella have shown that biallelic CFAP43 splice-site variants, including c.3661-2del, cause exon skipping, alter protein structure, and reduce expression, consistent with a role in motile cilia (PMID:32207550, PMID:29277146). However, these data derive from multiple morphological abnormalities of the sperm flagella rather than respiratory cilia. Overall, the genetic and experimental evidence for CFAP43 in PCD is limited. Additional biallelic case reports and ciliary functional assays in airway models are required. Key Take-home: CFAP43 variants may underlie PCD-like symptoms in isolated cases, but current evidence is insufficient for clinical implementation.
Gene–Disease AssociationLimitedSingle heterozygous proband with PCD-like features, no segregation, no biallelic cases Genetic EvidenceLimitedOne proband with heterozygous PTC variant; no AR biallelic mutations or additional cases Functional EvidenceLimitedSperm flagella studies of CFAP43 splice-site variant demonstrate exon skipping and structural alteration but not in respiratory cilia |