TY - JOUR
T1 - Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects
AU - Paff, Tamara
AU - Loges, Niki T.
AU - Aprea, Isabella
AU - Wu, Kaman
AU - Bakey, Zeineb
AU - Haarman, Eric G.
AU - Daniels, Johannes M.A.
AU - Sistermans, Erik A.
AU - Bogunovic, Natalija
AU - Dougherty, Gerard W.
AU - Höben, Inga M.
AU - Große-Onnebrink, Jörg
AU - Matter, Anja
AU - Olbrich, Heike
AU - Werner, Claudius
AU - Pals, Gerard
AU - Schmidts, Miriam
AU - Omran, Heymut
AU - Micha, Dimitra
PY - 2017/1/5
Y1 - 2017/1/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85009380914&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ajhg.2016.11.019
DO - https://doi.org/10.1016/j.ajhg.2016.11.019
M3 - Article
C2 - 28041644
SN - 0002-9297
VL - 100
SP - 160
EP - 168
JO - American journal of human genetics
JF - American journal of human genetics
IS - 1
ER -