부산대학교 도서관

Primary ciliary dyskinesia (PCD) is a rare disorder that affects the biogenesis or function of motile cilia resulting in chronic airway disease. PCD is genetically and phenotypically heterogeneous, with causative mutations identified in over 40 genes; however, the genetic basis of many cases is unknown. Using whole-exome sequencing, we identified three affected siblings with clinical symptoms of PCD but normal ciliary structure, carrying compound heterozygous loss-of-function variants in CFAP221. Computational analysis suggests that these variants are the most damaging alleles shared by all three siblings. Nasal epithelial cells from one of the subjects demonstrated slightly reduced beat frequency (16.5 Hz vs 17.7 Hz, p= 0.16); however, waveform analysis revealed that the CFAP221defective cilia beat in an aberrant circular pattern. These results show that genetic variants in CFAP221cause PCD and that CFAP221should be considered a candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.