TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport
Authors: Schmidts Miriam , Hou Yuqing , Cortés Claudio R. , Mans Dorus A. , Huber Celine , Boldt Karsten , Patel Mitali , van Reeuwijk Jeroen , Plaza Jean-Marc , van Beersum Sylvia E. C. , Yap Zhi Min , Letteboer Stef J. F. , Taylor S. Paige , Herridge Warren , Johnson Colin A. , Scambler Peter J. , Ueffing Marius , Kayserili Hulya , Krakow Deborah , King Stephen M. , Beales Philip L. , Al-Gazali Lihadh , Wicking Carol , Cormier-Daire Valerie , Roepman Ronald , Mitchison Hannah M. , Witman George B. ,   UK10K, Al-Turki Saeed , Anderson Carl , Anney Richard , Antony Dinu , Asimit Jennifer , Ayub Mohammad , Barrett Jeff , Barroso Inês , Bentham Jamie , Bhattacharya Shoumo , Blackwood Douglas , Bobrow Martin , Bochukova Elena , Bolton Patrick , Boustred Chris , Breen Gerome , Brion Marie-Jo , Brown Andrew , Calissano Mattia , Carss Keren , Chatterjee Krishna , Chen Lu , Cirak Sebhattin , Clapham Peter , Clement Gail , Coates Guy , Collier David , Cosgrove Catherine , Cox Tony , Craddock Nick , Crooks Lucy , Curran Sarah , Daly Allan , Danecek Petr , Smith George Davey , Day-Williams Aaron , Day Ian , Durbin Richard , Edkins Sarah , Ellis Peter , Evans David , Farooqi I. Sadaf , Fatemifar Ghazaleh , Fitzpatrick David , Flicek Paul , Floyd Jamie , Foley A. Reghan , Franklin Chris , Futema Marta , Gallagher Louise , Gaunt Tom , Geschwind Daniel , Greenwood Celia , Grozeva Detelina , Guo Xiaosen , Gurling Hugh , Hart Deborah , Hendricks Audrey , Holmans Peter , Huang Jie , Humphries Steve E. , Hurles Matt , Hysi Pirro , Jackson David , Jamshidi Yalda , Jewell David , Chris Joyce , Kaye Jane , Keane Thomas , Kemp John , Kennedy Karen , Kent Alastair , Kolb-Kokocinski Anja , Lachance Genevieve , Langford Cordelia , Lee Irene , Li Rui , Li Yingrui , Ryan Liu , Lönnqvist Jouko , Lopes Margarida , MacArthur Daniel G. , Massimo Mangino , Marchini Jonathan , Maslen John , McCarthy Shane , McGuffin Peter , McIntosh Andrew , McKechanie Andrew , McQuillin Andrew , Memari Yasin , Metrustry Sarah , Min Josine , Moayyeri Alireza , Morris James , Muddyman Dawn , Muntoni Francesco , Northstone Kate , O’Donovan Michael , O’Rahilly Stephen , Onoufriadis Alexandros , Oualkacha Karim , Owen Michael , Palotie Aarno , Panoutsopoulou Kalliope , Parker Victoria , Parr Jeremy , Paternoster Lavinia , Paunio Tiina , Payne Felicity , Perry John , Pietilainen Olli , Plagnol Vincent , Quail Michael A. , Quaye Lydia , Raymond Lucy , Rehnström Karola , Brent Richards J. , Ring Sue , Ritchie Graham R S , Savage David B. , Schoenmakers Nadia , Semple Robert K. , Serra Eva , Shihab Hashem , Shin So-Youn , Skuse David , Small Kerrin , Smee Carol , Soler Artigas María , Soranzo Nicole , Southam Lorraine , Spector Tim , St Pourcain Beate , St. Clair David , Stalker Jim , Surdulescu Gabriela , Suvisaari Jaana , Tachmazidou Ioanna , Tian Jing , Timpson Nic , Tobin Martin , Valdes Ana , van Kogelenberg Margriet , Vijayarangakannan Parthiban , Wain Louise , Walter Klaudia , Wang Jun , Ward Kirsten , Wheeler Ellie , Whittall Ros , Williams Hywel , Williamson Kathy , Wilson Scott G. , Wong Kim , Whyte Tamieka , ChangJiang Xu , Zeggini Eleftheria , Zhang Feng , Zheng Hou-Feng 
Published: June 2015

The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.