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

Eun Hye Cho, Hee Jae Huh, Inyoung Jeong, Nam Yong Lee, Won Jung Koh, Hae Chul Park, Chang Seok Ki

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)64-68
Number of pages5
JournalClinical Genetics
Volume98
Issue number1
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • NME5
  • central pair
  • motile cilia
  • primary ciliary dyskinesia
  • radial spokes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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