2. Academic Validation
  3. A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects

A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects

  • Clin Genet. 2020 Jul;98(1):64-68. doi: 10.1111/cge.13742.
Eun Hye Cho 1,  Hee Jae Huh 1,  Inyoung Jeong 2,  Nam Yong Lee 1,  Won-Jung Koh 3,  Hae-Chul Park 2,  Chang-Seok Ki 4
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • 2 Department of Biomedical Sciences, College of Medicine, Korea University, Ansan, South Korea.
  • 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • 4 GC Genome, Yongin, South Korea.
PMID: 32185794 DOI: 10.1111/cge.13742
Abstract

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.

Keywords

NME5; central pair; motile cilia; primary ciliary dyskinesia; radial spokes.

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