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A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects
Author(s) -
Cho Eun Hye,
Huh Hee Jae,
Jeong Inyoung,
Lee Nam Yong,
Koh WonJung,
Park HaeChul,
Ki ChangSeok
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13742
Subject(s) - primary ciliary dyskinesia , cilium , ciliopathy , morpholino , biology , ciliogenesis , motile cilium , ciliopathies , zebrafish , phenotype , microtubule , genetics , exome sequencing , dynein , microbiology and biotechnology , epiboly , nonsense , gene , medicine , embryogenesis , bronchiectasis , lung , gastrulation
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by defects in the function or structure of motitle cilia. In most cases, causative variants result in axonemal dynein arm anomalies, however, PCD due to radial spoke (RS) and central pair (CP) of microtubules has been rarely reported. To identify the molecular basis of PCD characterized by RS/CP defects, we performed whole exome sequencing in PCD patients with RS/CP defects. We identified a homozygous nonsense variant (c.572G>A; p.Trp191*) in NME5 , which encodes a protein component of the RS neck, in one PCD patient with situs solitus . Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. This is the first study to show NME5 as a PCD‐causative gene in humans. Our findings indicate that NME5 screening should be considered for PCD patients with RS/CP defects.