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X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

Title: X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
Authors: Olcese, C
Patel, MP
Shoemark, A
Kiviluoto, S
Legendre, M
Williams, HJ
Vaughan, CK
Hayward, J
Goldenberg, A
Emes, RD
Munye, MM
Dyer, L
Cahill, T
Bevillard, J
Gehrig, C
Guipponi, M
Chantot, S
Duquesnoy, P
Thomas, L
Jeanson, L
Copin, B
Tamalet, A
Thauvin-Robinet, C
Papon, J-F
Garin, A
Pin, I
Vera, G
Aurora, P
Fassad, MR
Jenkins, L
Boustred, C
Cullup, T
Dixon, M
Onoufriadis, A
Bush, A
Chung, EMK
Antonarakis, SE
Loebinger, MR
Wilson, R
Armengot, M
Escudier, E
Hogg, C
Amselem, S
Sun, Z
Bartoloni, L
Blouin, J-L
Mitchison, HM
Item Type: Journal Article
Abstract: By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2– DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.
Issue Date: 8-Feb-2017
Date of Acceptance: 15-Dec-2016
URI: http://hdl.handle.net/10044/1/53589
DOI: https://dx.doi.org/10.1038/ncomms14279
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 8
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2017
Sponsor/Funder: NIHR
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
OF-FUNCTION MUTATIONS
IDENTIFIES MUTATIONS
R2TP COMPLEX
DEFECTS
OUTER
PROTEIN
ARMS
VARIANTS
MOTILITY
INNER
UK10K Rare Group
MD Multidisciplinary
Publication Status: Published
Article Number: 14279
Appears in Collections:National Heart and Lung Institute