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

Tamara Paff, Niki T. Loges, Isabella Aprea, Kaman Wu, Zeineb Bakey, Eric G. Haarman, Johannes M.A. Daniels, Erik A. Sistermans, Natalija Bogunovic, Gerard W. Dougherty, Inga M. Höben, Jörg Große-Onnebrink, Anja Matter, Heike Olbrich, Claudius Werner, Gerard Pals, Miriam Schmidts, Heymut Omran, Dimitra Micha

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalAmerican journal of human genetics
Volume100
Issue number1
DOIs
Publication statusPublished - 5 Jan 2017

Cite this

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 ; Micha, Dimitra. / Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects. In: American journal of human genetics. 2017 ; Vol. 100, No. 1. pp. 160-168.
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title = "Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects",
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.",
author = "Tamara Paff and Loges, {Niki T.} and Isabella Aprea and Kaman Wu and Zeineb Bakey and Haarman, {Eric G.} and Daniels, {Johannes M.A.} and Sistermans, {Erik A.} and Natalija Bogunovic and Dougherty, {Gerard W.} and H{\"o}ben, {Inga M.} and J{\"o}rg Gro{\ss}e-Onnebrink and Anja Matter and Heike Olbrich and Claudius Werner and Gerard Pals and Miriam Schmidts and Heymut Omran and Dimitra Micha",
year = "2017",
month = "1",
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doi = "10.1016/j.ajhg.2016.11.019",
language = "English",
volume = "100",
pages = "160--168",
journal = "American journal of human genetics",
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Paff, T, Loges, NT, Aprea, I, Wu, K, Bakey, Z, Haarman, EG, Daniels, JMA, Sistermans, EA, Bogunovic, N, Dougherty, GW, Höben, IM, Große-Onnebrink, J, Matter, A, Olbrich, H, Werner, C, Pals, G, Schmidts, M, Omran, H & Micha, D 2017, 'Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects' American journal of human genetics, vol. 100, no. 1, pp. 160-168. https://doi.org/10.1016/j.ajhg.2016.11.019

Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects. / 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; Micha, Dimitra.

In: American journal of human genetics, Vol. 100, No. 1, 05.01.2017, p. 160-168.

Research output: Contribution to journalArticleAcademicpeer-review

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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.

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DO - 10.1016/j.ajhg.2016.11.019

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JO - American journal of human genetics

JF - American journal of human genetics

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