X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
Chiara Olcese
(1)
,
Mitali Patel
(2)
,
Amelia Shoemark
(3)
,
Santeri Kiviluoto
(4)
,
Marie Legendre
(5, 6)
,
Hywel Williams
(2)
,
Cara Vaughan
(7)
,
Jane Hayward
(2)
,
Alice Goldenberg
(8)
,
Richard Emes
(9)
,
Mustafa Munye
(2)
,
Laura Dyer
(2)
,
Thomas Cahill
(3)
,
Jeremy Bevillard
(1)
,
Corinne Gehrig
(1)
,
Michel Guipponi
(1, 10)
,
Sandra Chantot
(5, 6)
,
Philippe Duquesnoy
(5, 6)
,
Lucie Thomas
(5, 6)
,
Ludovic Jeanson
(5, 6)
,
Bruno Copin
(5, 6)
,
Aline Tamalet
(6)
,
Christel Thauvin-Robinet
(11, 12)
,
Jean- François Papon
(13)
,
Antoine Garin
(13)
,
Isabelle Pin
(14)
,
Paul Aurora
(8)
,
Mahmoud Fassad
(2, 15)
,
Lucy Jenkins
(16)
,
Christopher Boustred
(16)
,
Thomas Cullup
(16)
,
Mellisa Dixon
(3)
,
Alexandros Onoufriadis
(17)
,
Andrew Bush
(3, 18)
,
Eddie Chung
(2)
,
Stylianos Antonarakis
(1, 10, 19)
,
Michael Loebinger
(3)
,
Robert Wilson
(3)
,
Miguel Armengot
(20)
,
Estelle Escudier
(5, 6)
,
Claire Hogg
(3)
,
Serge Amselem
(5, 6)
,
Zhaoxia Sun
(4)
,
Lucia Bartoloni
(1)
,
Jean-Louis Blouin
(1, 10)
,
Hannah Mitchison
(2)
1
UNIGE -
Université de Genève = University of Geneva
2 UCL - Great Ormond Street Institute of Child Health
3 Royal Brompton Hospital
4 Yale University School of Medicine
5 U933 - Maladies génétiques d'expression pédiatrique
6 CHU Trousseau [APHP]
7 Birkbeck College [University of London]
8 GMFC - Génétique du cancer et des maladies neuropsychiatriques
9 UON - University of Nottingham, UK
10 HUG - Geneva University Hospital
11 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
12 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
13 Service d’ORL et de chirurgie cervico-faciale [CHU Le Kremlin-Bicêtre]
14 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
15 Alexandria University [Alexandrie]
16 GOSHC - Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK]
17 King‘s College London
18 Imperial College London
19 iGE3 - Institute of Genetics and Genomics in Geneva
20 UV - Universitat de València
2 UCL - Great Ormond Street Institute of Child Health
3 Royal Brompton Hospital
4 Yale University School of Medicine
5 U933 - Maladies génétiques d'expression pédiatrique
6 CHU Trousseau [APHP]
7 Birkbeck College [University of London]
8 GMFC - Génétique du cancer et des maladies neuropsychiatriques
9 UON - University of Nottingham, UK
10 HUG - Geneva University Hospital
11 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
12 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
13 Service d’ORL et de chirurgie cervico-faciale [CHU Le Kremlin-Bicêtre]
14 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
15 Alexandria University [Alexandrie]
16 GOSHC - Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK]
17 King‘s College London
18 Imperial College London
19 iGE3 - Institute of Genetics and Genomics in Geneva
20 UV - Universitat de València
Marie Legendre
- Fonction : co premier-auteur
- PersonId : 1147534
- IdHAL : marie-legendre
- ORCID : 0000-0003-2178-0846
Sandra Chantot
- Fonction : Auteur
- PersonId : 1182915
- IdHAL : sandra-chantot-bastaraud
- ORCID : 0000-0001-6446-3504
- IdRef : 090950348
Lucie Thomas
- Fonction : Auteur
- PersonId : 1173664
- IdHAL : lucie-thomas
- ORCID : 0000-0001-6998-590X
- IdRef : 270380582
Bruno Copin
- Fonction : Auteur
- PersonId : 1176543
- IdHAL : bruno-copin
Estelle Escudier
- Fonction : Auteur
- PersonId : 1213534
- IdHAL : estelle-escudier
- ORCID : 0000-0002-1569-8072
- IdRef : 033701997
Serge Amselem
- Fonction : co dernier-auteur
- PersonId : 936326
- IdHAL : serge-amselem
- ORCID : 0000-0001-9506-3968
- IdRef : 066957761
Jean-Louis Blouin
- Fonction : co dernier-auteur
Résumé
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 DNAAF2DNAAF4- 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.