A nonsense variant inNME5causes human primary ciliary dyskinesia with radial spoke defects

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*) inNME5, which encodes a protein component of the RS neck, in one PCD patient withsitus solitus. Morpholino knockdown ofnme5in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. This is the first study to showNME5as a PCD-causative gene in humans. Our findings indicate thatNME5screening should be considered for PCD patients with RS/CP defects.