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

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Listed:
  • Chiara Olcese

    (University of Geneva School of Medicine
    University of Ferrara)

  • Mitali P. Patel

    (Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Amelia Shoemark

    (Royal Brompton Hospital)

  • Santeri Kiviluoto

    (Yale University School of Medicine)

  • Marie Legendre

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Hywel J. Williams

    (GOSgene, Genetics and Genomic Medicine Programme, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Cara K. Vaughan

    (Institute of Structural and Molecular Biology, University College London and Birkbeck College, Biological Sciences)

  • Jane Hayward

    (Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Alice Goldenberg

    (Service de Génétique, CHU de Rouen, INSERM U1079, Université de Rouen, Centre Normand de Génomique Médicale et Médecine Personnalisée)

  • Richard D. Emes

    (School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus
    Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington Campus)

  • Mustafa M. Munye

    (Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Laura Dyer

    (Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Thomas Cahill

    (Royal Brompton Hospital)

  • Jeremy Bevillard

    (University of Geneva School of Medicine)

  • Corinne Gehrig

    (University of Geneva School of Medicine)

  • Michel Guipponi

    (University of Geneva School of Medicine
    University Hospitals of Geneva)

  • Sandra Chantot

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Philippe Duquesnoy

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Lucie Thomas

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Ludovic Jeanson

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Bruno Copin

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Aline Tamalet

    (Service de Pneumologie Pédiatrique, Centre National de Référence des Maladies Respiratoires Rares, Hôpital Armand-Trousseau, AP-HP)

  • Christel Thauvin-Robinet

    (Centre de génétique, CHU Dijon Bourgogne, Équipe EA4271 GAD, Université de Bourgogne, Hôpital François Mitterrand)

  • Jean- François Papon

    (Service d’Oto-Rhino-Laryngologie et de Chirurgie Cervico-Maxillo-Faciale, Hôpital Bicêtre, AP-HP)

  • Antoine Garin

    (Service d’Oto-Rhino-Laryngologie et de Chirurgie Cervico-Maxillo-Faciale, Hôpital Bicêtre, AP-HP)

  • Isabelle Pin

    (Pédiatrie, CHU Grenoble Alpes, INSERM U 1209, Institut for Advanced Biosciences, Université Grenoble Alpes)

  • Gabriella Vera

    (Service de Génétique, CHU de Rouen, INSERM U1079, Université de Rouen, Centre Normand de Génomique Médicale et Médecine Personnalisée)

  • Paul Aurora

    (Great Ormond Street Hospital for Children
    Critical Care and Anaesthesia Unit, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Mahmoud R. Fassad

    (Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health
    Medical Research Institute, Alexandria University)

  • Lucy Jenkins

    (North East Thames Regional Genetics Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, Queen Square)

  • Christopher Boustred

    (North East Thames Regional Genetics Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, Queen Square)

  • Thomas Cullup

    (North East Thames Regional Genetics Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, Queen Square)

  • Mellisa Dixon

    (Royal Brompton Hospital)

  • Alexandros Onoufriadis

    (King's College London School of Medicine, Guy's Hospital)

  • Andrew Bush

    (Royal Brompton Hospital
    National Heart and Lung Institute, Imperial College London)

  • Eddie M. K. Chung

    (Population, Policy and Practice, University College London (UCL) Great Ormond Street Institute of Child Health)

  • Stylianos E. Antonarakis

    (University of Geneva School of Medicine
    University Hospitals of Geneva
    Institute of Genetics and Genomics in Geneva, iGE3)

  • Michael R. Loebinger

    (Host Defence Unit, Respiratory Medicine, Royal Brompton Hospital)

  • Robert Wilson

    (Host Defence Unit, Respiratory Medicine, Royal Brompton Hospital)

  • Miguel Armengot

    (Rhinology and Primary Ciliary Dyskinesia Unit, General and University Hospital, Medical School, Valencia University)

  • Estelle Escudier

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Claire Hogg

    (Royal Brompton Hospital)

  • Serge Amselem

    (Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S933 and Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP)

  • Zhaoxia Sun

    (Yale University School of Medicine)

  • Lucia Bartoloni

    (University of Geneva School of Medicine
    UOSD Laboratorio Analisi Venezia, ULSS12 Veneziana)

  • Jean-Louis Blouin

    (University of Geneva School of Medicine
    University Hospitals of Geneva)

  • Hannah M. Mitchison

    (Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health)

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.

Suggested Citation

  • Chiara Olcese & Mitali P. Patel & Amelia Shoemark & Santeri Kiviluoto & Marie Legendre & Hywel J. Williams & Cara K. Vaughan & Jane Hayward & Alice Goldenberg & Richard D. Emes & Mustafa M. Munye & La, 2017. "X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14279
    DOI: 10.1038/ncomms14279
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