PUBLICATION
TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport
- Authors
- Schmidts, M., Hou, Y., Cortés, C.R., Mans, D.A., Huber, C., Boldt, K., Patel, M., van Reeuwijk, J., Plaza, J.M., van Beersum, S.E., Yap, Z.M., Letteboer, S.J., Taylor, S.P., Herridge, W., Johnson, C.A., Scambler, P.J., Ueffing, M., Kayserili, H., Krakow, D., King, S.M., Beales, P.L., Al-Gazali, L., Wicking, C., Cormier-Daire, V., Roepman, R., Mitchison, H.M., Witman, G.B.
- ID
- ZDB-PUB-170214-174
- Date
- 2015
- Source
- Nature communications 6: 7074 (Journal)
- Registered Authors
- Keywords
- Cell signalling, Disease genetics, Mutation, Paediatric rheumatic diseases
- MeSH Terms
-
- Animals
- Chlamydomonas reinhardtii
- Dyneins/genetics*
- Ellis-Van Creveld Syndrome/genetics*
- Flagella/physiology*
- Gene Knockdown Techniques
- HEK293 Cells
- Humans
- Mice
- Mutation
- Penetrance
- Zebrafish
- PubMed
- 26044572 Full text @ Nat. Commun.
Citation
Schmidts, M., Hou, Y., Cortés, C.R., Mans, D.A., Huber, C., Boldt, K., Patel, M., van Reeuwijk, J., Plaza, J.M., van Beersum, S.E., Yap, Z.M., Letteboer, S.J., Taylor, S.P., Herridge, W., Johnson, C.A., Scambler, P.J., Ueffing, M., Kayserili, H., Krakow, D., King, S.M., Beales, P.L., Al-Gazali, L., Wicking, C., Cormier-Daire, V., Roepman, R., Mitchison, H.M., Witman, G.B. (2015) TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. Nature communications. 6:7074.
Abstract
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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-40.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping