%0 Journal Article
%T Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects
%A Anja Matter
%A Claudius Werner
%A Eric G. Haarman
%A Erik A. Sistermans
%A Gerard Pals
%A Gerard W. Dougherty
%A Heike Olbrich
%A Heymut Omran
%A Inga M. H£¿ben
%A Isabella Aprea
%A Johannes M.A. Daniels
%A J£¿rg Gro£¿e-Onnebrink
%A Kaman Wu
%A Miriam Schmidts
%A Natalija Bogunovic
%A Niki T. Loges
%A Tamara Paff
%A Zeineb Bakey
%J Archive of "American Journal of Human Genetics".
%D 2017
%R 10.1016/j.ajhg.2016.11.019
%X 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
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223094/