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

TitleIdentification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia.
Publication TypeJournal Article
Year of Publication2020
AuthorsBustamante-Marin, XM, Shapiro, A, Sears, PR, Charng, W-L, Conrad, DF, Leigh, MW, Knowles, MR, Ostrowski, LE, Zariwala, MA
JournalJ Hum Genet
Volume65
Issue2
Pagination175-180
Date Published2020 Jan
ISSN1435-232X
Abstract

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.

DOI10.1038/s10038-019-0686-1
Alternate JournalJ. Hum. Genet.
PubMed ID31636325
PubMed Central IDPMC6920546
Grant ListP51 OD011092 / OD / NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
5U54HL096458 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01 MH101810 / MH / NIMH NIH HHS / United States
R01 HD078641 / HD / NICHD NIH HHS / United States
U54 HL096458 / HL / NHLBI NIH HHS / United States
R01HD078641 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01 HL117836 / HL / NHLBI NIH HHS / United States
R01 HL071798 / HL / NHLBI NIH HHS / United States
T32-MH014677 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
T32 MH014677 / MH / NIMH NIH HHS / United States
UL1 TR000083 / TR / NCATS NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States
P30 DK065988 / DK / NIDDK NIH HHS / United States
S10 OD018521 / OD / NIH HHS / United States
R01MH101810 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
U54 HG006504 / HG / NHGRI NIH HHS / United States
R01HL117836 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
UM1HG006504 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01HL071798 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /