Mutations in PIH1 D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects

作者：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; Hoeben Inga M; Grosse Onnebrink Jorg; Matter Anja; Olbrich Heike; Werner Claudius; Pals Gerard; Schmidts Miriam; Omran Heymut; Micha Dimitra^*

来源：American Journal of Human Genetics, 2017, 100(1): 160-168.

DOI：10.1016/j.ajhg.2016.11.019

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. PIN1D3 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 ODA5 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.

• 出版日期2017-1-5