Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia

Ximena M. Bustamante-Marin, Adam Shapiro, Patrick R. Sears, Wu Lin Charng, Donald F. Conrad, Margaret W. Leigh, Michael R. Knowles, Lawrence E. Ostrowski, Maimoona A. Zariwala

Research output: Contribution to journalArticle

2 Scopus citations


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 CFAP221 defective cilia beat in an aberrant circular pattern. These results show that genetic variants in CFAP221 cause PCD and that CFAP221 should be considered a candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.

Original languageEnglish (US)
Pages (from-to)175-180
Number of pages6
JournalJournal of Human Genetics
Issue number2
StatePublished - Jan 1 2020


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bustamante-Marin, X. M., Shapiro, A., Sears, P. R., Charng, W. L., Conrad, D. F., Leigh, M. W., Knowles, M. R., Ostrowski, L. E., & Zariwala, M. A. (2020). Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia. Journal of Human Genetics, 65(2), 175-180.