Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects

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• 作者：Tamara Paff¹ ; ² ; ³ ; ⁸ ; Niki T. Loges⁴ ; ⁸ ; Isabella Aprea⁴ ; Kaman Wu⁵ ; Zeineb Bakey⁵ ; Eric G. Haarman² ; Johannes M.A. Daniels¹ ; Erik A. Sistermans³ ; Natalija Bogunovic⁶ ; Gerard W. Dougherty⁴ ; Inga M. Hö ; ben⁴ ; Jö ; rg Groß ; e-Onnebrink⁴ ; Anja Matter⁴ ; Heike Olbrich⁴ ; Claudius Werner⁴ ; Gerard Pals³ ; Miriam Schmidts⁵ ; ⁷ ; ⁸ ; Heymut Omran⁴ ; ⁸ ; Dimitra Micha³ ; ⁸ ; ^{d.micha@vumc.nl}
• 刊名：The American Journal of Human Genetics
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：100
• 期：1
• 页码：160-168
• 全文大小：2019 K
• 卷排序：100

文摘

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.