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

被引：115

作者：

Olcese, Chiara ^{[1
,2
]}

Patel, Mitali P. ^{[3
]}

Shoemark, Amelia ^{[4
]}

Kiviluoto, Santeri ^{[5
]}

Legendre, Marie ^{[6
,7
]}

Williams, Hywel J. ^{[8
]}

Vaughan, Cara K. ^{[9
,10
]}

Hayward, Jane ^{[3
]}

Goldenberg, Alice ^{[11
]}

Emes, Richard D. ^{[12
,13
]}

Munye, Mustafa M. ^{[3
]}

Dyer, Laura ^{[3
]}

Cahill, Thomas ^{[4
]}

Bevillard, Jeremy ^{[1
]}

Gehrig, Corinne ^{[1
]}

Guipponi, Michel ^{[1
,14
]}

Chantot, Sandra ^{[6
,7
]}

Duquesnoy, Philippe ^{[6
,7
]}

Thomas, Lucie ^{[6
,7
]}

Jeanson, Ludovic ^{[6
,7
]}

Copin, Bruno ^{[6
,7
]}

Tamalet, Aline ^{[15
]}

Thauvin-Robinet, Christel ^{[16
]}

Papon, Jean-Francois ^{[17
]}

Garin, Antoine ^{[17
]}

Pin, Isabelle ^{[18
]}

Vera, Gabriella

Aurora, Paul ^{[19
,20
]}

Fassad, Mahmoud R. ^{[21
]}

Jenkins, Lucy ^{[22
]}

Boustred, Christopher ^{[22
]}

Cullup, Thomas ^{[22
]}

Dixon, Mellisa ^{[4
]}

Onoufriadis, Alexandros ^{[23
]}

Bush, Andrew ^{[24
]}

Chung, Eddie M. K. ^{[25
]}

Antonarakis, Stylianos E. ^{[14
,26
]}

Loebinger, Michael R. ^{[27
]}

Wilson, Robert ^{[27
]}

Armengot, Miguel ^{[28
]}

Escudier, Estelle ^{[6
,7
]}

Hogg, Claire ^{[4
]}

Amselem, Serge ^{[6
,7
]}

Sun, Zhaoxia ^{[5
]}

Bartoloni, Lucia ^{[29
]}

Blouin, Jean-Louis ^{[14
]}

Mitchison, Hannah M. ^{[3
]}

机构：

[1] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[2] Univ Ferrara, Dept Life Sci & Biotechnol, I-44121 Ferrara, Italy

[3] UCL, Genet & Genom Med, Inst Child Hlth, Great Ormond St,Guilford St, London WC1N 1EH, England

[4] Royal Brompton Hosp, Dept Paediat, Sydney St, London SW3 6NP, England

[5] Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA

[6] UPMC Univ Paris 06, Sorbonne Univ, Hop Armand Trousseau, AP HP,INSERM UMR S933, F-75012 Paris, France

[7] UPMC Univ Paris 06, Sorbonne Univ, Hop Armand Trousseau, AP HP,Serv Genet & Embryol Med, F-75012 Paris, France

[8] UCL, Inst Child Hlth, Genet & Genom Med Programme, GOSgene, Great Ormond St,30 Guilford St, London WC1N 1EH, England

[9] UCL, Inst Struct & Mol Biol, Malet St, London WC1E 7HX, England

[10] Birkbeck Coll, Biol Sci, Malet St, London WC1E 7HX, England

[11] Univ Rouen, CHU Rouen, INSERM U1079, Serv Genet,Ctr Normand Genom Med & Med Personnali, Rouen, France

[12] Univ Nottingham, Sch Vet Med & Sci, Sutton Bonington Campus, Loughborough LE12 5RD, Leics, England

[13] Univ Nottingham, Adv Data Anal Ctr, Sutton Bonington Campus, Loughborough LE12 5RD, Leics, England

[14] Univ Hosp Geneva, Dept Genet Med & Lab, CH-1211 Geneva, Switzerland

[15] Hop Armand Trousseau, AP HP, Ctr Natl Reference Malad Resp Rares, Serv Pneumol Pediat, F-75012 Paris, France

[16] Univ Bourgogne, CHU Dijon Bourgogne, Hop Francois Mitterrand, Ctr Genet,Equipe GAD EA4271, F-21000 Dijon, France

[17] Hop Bicetre, AP HP, Serv Otorhinolaryngol & Chirurg Cerv Maxillofacia, F-94275 Le Kremlin Bicetre, France

[18] Univ Grenoble Alpes, Inst Adv Biosci, CHU Grenoble Alpes, Pediat,INSERM U1209, Grenoble, France

[19] Hosp Children, Dept Paediat Resp Med, Great Ormond St, London WC1N 3JH, England

[20] UCL, Inst Child Hlth, Crit Care & Anaesthesia Unit, Dept Resp, Great Ormond St,Guilford St, London WC1N 1EH, England

[21] Univ Alexandria, Med Res Inst, Dept Human Genet, El Hadra Alexandria 21561, Egypt

[22] Hosp Children NHS Fdn Trust, North East Thames Reg Genet Lab, Great Ormond St,Queen Sq, London WC1N 3BH, England

[23] Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet,Div Genet & Mol Med, London SE1 9RT, England

[24] Imperial Coll London, Natl Heart & Lung Inst, Dept Paediat Resp Med, London SW3 6LR, England

[25] UCL, Populat Policy & Practice, Inst Child Hlth, Great Ormond St,Guilford St, London WC1N 1EH, England

[26] iGE3, Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland

[27] Royal Brompton Hosp, Resp Med, Host Def Unit, London SW3 6NP, England

[28] Univ Valencia, Rhinol & Primary Ciliary Dyskinesia Unit, Gen & Univ Hosp, Sch Med, E-46014 Valencia, Spain

[29] UOSD, Lab Anal Venezia, Veneziana ULSS12, I-30121 Venice, Italy

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

瑞士国家科学基金会; 英国惠康基金; 美国国家卫生研究院;

关键词：

OF-FUNCTION MUTATIONS; IDENTIFIES MUTATIONS; R2TP COMPLEX; OUTER; DEFECTS; VARIANTS; INNER; VISUALIZATION; MECHANISMS; MOTILITY;

D O I：

10.1038/ncomms14279

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 63 条

[31] Deletions and Point Mutations of LRRC50 Cause Primary Ciliary Dyskinesia Due to Dynein Arm Defects [J].

Loges, Niki Tomas ;

Olbrich, Heike ;

Becker-Heck, Anita ;

Haeffner, Karsten ;

Heer, Angelina ;

Reinhard, Christina ;

Schmidts, Miriam ;

Kispert, Andreas ;

Zariwal, Maimoona A. ;

Leigh, Margaret W. ;

Knowles, Michael R. ;

Zentgraf, Hanswalter ;

Seithe, Horst ;

Nuernberg, Gudrun ;

Nuernberg, Peter ;

Reinhardt, Richard ;

Omran, Heymut .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (06) :883-889

[32] Diagnosis and management of primary ciliary dyskinesia [J].

Lucas, Jane S. ;

Burgess, Andrea ;

Mitchison, Hannah M. ;

Moya, Eduardo ;

Williamson, Michael ;

Hogg, Claire .

ARCHIVES OF DISEASE IN CHILDHOOD, 2014, 99 (09) :850-856

[33] Mechanisms of Otoconia and Otolith Development [J].

Lundberg, Yunxia Wang ;

Xu, Yinfang ;

Thiessen, Kevin D. ;

Kramer, Kenneth L. .

DEVELOPMENTAL DYNAMICS, 2015, 244 (03) :239-253

[34] Dual-axis tomography: An approach with alignment methods that preserve resolution [J].

Mastronarde, DN .

JOURNAL OF STRUCTURAL BIOLOGY, 1997, 120 (03) :343-352

[35] Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor [J].

McLaren, William ;

Pritchard, Bethan ;

Rios, Daniel ;

Chen, Yuan ;

Flicek, Paul ;

Cunningham, Fiona .

BIOINFORMATICS, 2010, 26 (16) :2069-2070

[36] Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia [J].

Mitchison, Hannah M. ;

Schmidts, Miriam ;

Loges, Niki T. ;

Freshour, Judy ;

Dritsoula, Athina ;

Hirst, Rob A. ;

O'Callaghan, Christopher ;

Blau, Hannah ;

Al Dabbagh, Maha ;

Olbrich, Heike ;

Beales, Philip L. ;

Yagi, Toshiki ;

Mussaffi, Huda ;

Chung, Eddie M. K. ;

Omran, Heymut ;

Mitchell, David R. .

NATURE GENETICS, 2012, 44 (04) :381-U186

[37] RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa [J].

Moore, A ;

Escudier, E ;

Roger, G ;

Tamalet, A ;

Pelosse, B ;

Marlin, S ;

Clément, A ;

Geremek, M ;

Delaisi, B ;

Bridoux, AM ;

Coste, A ;

Witt, M ;

Duriez, B ;

Amselem, S .

JOURNAL OF MEDICAL GENETICS, 2006, 43 (04) :326-333

[38] Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia [J].

Moore, Daniel J. ;

Onoufriadis, Alexandros ;

Shoemark, Amelia ;

Simpson, Michael A. ;

zur Lage, Petra I. ;

de Castro, Sandra C. ;

Bartoloni, Lucia ;

Gallone, Giuseppe ;

Petridi, Stavroula ;

Woollard, Wesley J. ;

Antony, Dinu ;

Schmidts, Miriam ;

Didonna, Teresa ;

Makrythanasis, Periklis ;

Bevillard, Jeremy ;

Mongan, Nigel P. ;

Djakow, Jana ;

Pals, Gerard ;

Lucas, Jane S. ;

Marthin, June K. ;

Nielsen, Kim G. ;

Santoni, Federico ;

Guipponi, Michel ;

Hogg, Claire ;

Antonarakis, Stylianos E. ;

Emes, Richard D. ;

Chung, Eddie M. K. ;

Greene, Nicholas D. E. ;

Blouin, Jean-Louis ;

Jarman, Andrew P. ;

Mitchison, Hannah M. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 93 (02) :346-356

[39] UNUSUAL INHERITANCE OF PRIMARY CILIARY DYSKINESIA (KARTAGENERS-SYNDROME) [J].

NARAYAN, D ;

KRISHNAN, SN ;

UPENDER, M ;

RAVIKUMAR, TS ;

MAHONEY, MJ ;

DOLAN, TF ;

TEEBI, AS ;

HADDAD, GG .

JOURNAL OF MEDICAL GENETICS, 1994, 31 (06) :493-496

[40] The molecular architecture of axonemes revealed by cryoelectron tomography [J].

Nicastro, Daniela ;

Schwartz, Cindi ;

Pierson, Jason ;

Gaudette, Richard ;

Porter, Mary E. ;

McIntosh, J. Richard .

SCIENCE, 2006, 313 (5789) :944-948

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