1. Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects.
- Author
-
Paff, Tamara, Loges, Niki T., Aprea, Isabella, Wu, Kaman, Bakey, Zeineb, Haarman, Eric G., Daniels, Johannes M.A., Sistermans, Erik A., Bogunovic, Natalija, Dougherty, Gerard W., Höben, Inga M., Große-Onnebrink, Jörg, Matter, Anja, Olbrich, Heike, Werner, Claudius, Pals, Gerard, Schmidts, Miriam, Omran, Heymut, and Micha, Dimitra
- Subjects
- *
CILIARY motility disorders , *DYNEIN , *ARM diseases , *GENETIC mutation , *PHENOTYPES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF