Clinical and Genetic Study of a Pseudo-Dominant Primary Ciliary Dyskinesia Pedigree: The First DNAAF1-Associated Family Reported in Chinese Population.

backgroundPrimary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder typically inherited in an autosomal recessive pattern. Pseudo-dominant inheritance is exceptionally uncommon and remains poorly characterized in PCD.

methodsWe conducted a clinical and genetic study of a non-consanguineous Chinese PCD pedigree with four affected individuals across two generations. Whole exome sequencing and Sanger sequencing were performed to identify pathogenic variants.

resultsTwo variants in DNAAF1, c.1930A>T (p.Arg644Ter) and c.1022_1023del (p.Gln341ArgfsTer10), were identified and shown to co-segregate with the disease in a pseudo-dominant pattern. The proband, her brother, and her two naturally conceived sons were all affected, with her parents and husband being unaffected carriers. Transmission electron microscopy revealed absence of both outer and inner dynein arms, and high-speed video analysis demonstrated immotile or severely reduced ciliary beating. Intrafamilial phenotypic variability was notable, including distinct laterality defects (situs inversus, heterotaxy, and situs solitus) and varying degrees of pulmonary involvement.

conclusionOur report provides the first description of pseudo-dominant inheritance in PCD and expands the knowledge of the disease by offering detailed clinical and ciliary phenotyping.