PUBLICATION
A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects
- Authors
- Cho, E.H., Huh, H.J., Jeong, I., Lee, N.Y., Koh, W.J., Park, H.C., Ki, C.S.
- ID
- ZDB-PUB-200403-112
- Date
- 2020
- Source
- Clinical genetics 98(1): 64-68 (Journal)
- Registered Authors
- Jeong, Inyoung, Park, Hae-Chul
- Keywords
- NME5, central pair, motile cilia, primary ciliary dyskinesia, radial spokes
- MeSH Terms
-
- Adult
- Amino Acid Sequence
- Animals
- Axonemal Dyneins/genetics
- Axoneme/genetics
- Cilia/genetics*
- Ciliary Motility Disorders/genetics*
- Codon, Nonsense/genetics*
- Female
- Homozygote
- Humans
- Microtubules/genetics
- Mutation/genetics*
- NM23 Nucleoside Diphosphate Kinases/genetics*
- Phenotype
- Zebrafish/genetics
- PubMed
- 32185794 Full text @ Clin. Genet.
Citation
Cho, E.H., Huh, H.J., Jeong, I., Lee, N.Y., Koh, W.J., Park, H.C., Ki, C.S. (2020) A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects. Clinical genetics. 98(1):64-68.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping