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Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2017 Jan 05; Vol. 100 (1), pp. 160-168. Date of Electronic Publication: 2016 Dec 29. - Publication Year :
- 2017
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Abstract
- Defects in motile cilia and sperm flagella cause primary ciliary dyskinesia (PCD), characterized by chronic airway disease, infertility, and left-right body axis disturbance. Here we report maternally inherited and de novo mutations in PIH1D3 in four men affected with PCD. PIH1D3 is located on the X chromosome and is involved in the preassembly of both outer (ODA) and inner (IDA) dynein arms of cilia and sperm flagella. Loss-of-function mutations in PIH1D3 lead to absent ODAs and reduced to absent IDAs, causing ciliary and flagellar immotility. Further, PIH1D3 interacts and co-precipitates with cytoplasmic ODA/IDA assembly factors DNAAF2 and DNAAF4. This result has clinical and genetic counseling implications for genetically unsolved male case subjects with a classic PCD phenotype that lack additional phenotypes such as intellectual disability or retinitis pigmentosa.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cilia metabolism
Ciliary Motility Disorders metabolism
Ciliary Motility Disorders pathology
Cytoplasm metabolism
Female
Humans
Male
Pedigree
Phenotype
Sperm Motility genetics
Sperm Tail metabolism
Cilia pathology
Ciliary Motility Disorders genetics
Dyneins metabolism
Genes, X-Linked
Mutation genetics
Sperm Tail pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 100
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 28041644
- Full Text :
- https://doi.org/10.1016/j.ajhg.2016.11.019