TY - JOUR
T1 - Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia
AU - Bustamante-Marin, Ximena M.
AU - Shapiro, Adam
AU - Sears, Patrick R.
AU - Charng, Wu Lin
AU - Conrad, Donald F.
AU - Leigh, Margaret W.
AU - Knowles, Michael R.
AU - Ostrowski, Lawrence E.
AU - Zariwala, Maimoona A.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s10038-019-0686-1
DO - 10.1038/s10038-019-0686-1
M3 - Article
C2 - 31636325
AN - SCOPUS:85074203030
SN - 1434-5161
VL - 65
SP - 175
EP - 180
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 2
ER -