TCTEX1D2突变是伴有逆向纤毛内运输受损的Jeune窒息性胸廓发育不良的病因。
TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport.
作者信息
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
机构信息
1] Genetics and Genomic Medicine Programme, University College London (UCL), Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK [2] Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands [3] Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands [4] Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Mathildenstrasse 1, 79112 Freiburg, Germany.
Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
出版信息
Nat Commun. 2015 Jun 5;6:7074. doi: 10.1038/ncomms8074.
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.
对纤毛软骨发育异常个体的分析能够揭示控制纤毛发生和细胞信号传导的敏感机制，这些机制对于胚胎发育和生存至关重要。在此，我们鉴定出导致具有部分显性遗传的Jeune窒息性胸廓发育不良的TCTEX1D2突变。TCTEX1D2的缺失会损害人类和原生生物衣藻中的逆向鞭毛内运输（IFT），同时伴随着逆向IFT动力蛋白的不稳定。因此，我们将TCTEX1D2定义为进化保守的逆向IFT机制的一个组成部分。它与几种IFT动力蛋白轻链结合，是脊椎动物正确骨骼形成所必需的，但在某些条件下可能在功能上是冗余的。
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