Abstract
Jeune asphyxiating thoracic dystrophy, an autosomal recessive chondrodysplasia, often leads to death in infancy because of a severely constricted thoracic cage and respiratory insufficiency; retinal degeneration, cystic renal disease and polydactyly may be complicating features. We show that IFT80 mutations underlie a subset of Jeune asphyxiating thoracic dystrophy cases, establishing the first association of a defective intraflagellar transport (IFT) protein with human disease. Knockdown of ift80 in zebrafish resulted in cystic kidneys, and knockdown in Tetrahymena thermophila produced shortened or absent cilia.
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Badano, J.L., Mitsuma, N., Beales, P.L. & Katsanis, N. Annu. Rev. Genomics Hum. Genet. 7, 125–148 (2006).
Li, J.B. et al. Cell 117, 541–552 (2004).
Efimenko, E. et al. Development 132, 1923–1934 (2005).
Kunitomo, H., Uesugi, H., Kohara, Y. & Lino, Y. Genome Biol. 6, R17 (2005).
Blacque, O.E. et al. Genes Dev. 18, 1630–1642 (2004).
Ou, G. et al. Nature 436, 583–587 (2005).
Rosenbaum, J.L. & Witman, G.B. Nat. Rev. Mol. Cell Biol. 3, 813–825 (2002).
Collins, K. & Gorovsky, M.A. Curr. Biol. 15, R317–R318 (2005).
Sun, Z. et al. Development 131, 4085–4093 (2004).
Haycraft, C.J. et al. PLoS Genet. 1, e53 (2005).
May, S.R. et al. Dev. Biol. 287, 378–389 (2005).
Liu, A., Wang, B. & Niswander, L.A. Development 132, 3103–3111 (2005).
Wada, N. et al. Development 132, 3977–3988 (2005).
Haycraft, C.J. et al. Development 134, 307–316 (2007).
Acknowledgements
We thank F. Goodman for initiating the project and the many families and clinicians who have provided material and information for the project. In particular, C. Hall provided interpretations of the skeletal surveys, and R. Howard-Till, D. Chalker, J. Frankel and M.C. Yao provided help, plasmids and reagents. This work was supported by Newlife (P.J.S., P.L.B.), the Wellcome Trust (P.L.B.), the UK Medical Research Council (J.L.T.) and the British Heart Foundation (P.J.S.). C.G.P. is supported by the Damon Runyon Cancer Research Foundation (1879-05), and M.W. is supported by a grant from the US National Institutes of Health (GM074746).
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P.L.B. devised and conducted the bioinformatic analysis, contributed to the experimental plan and edited the paper. N.E., B.T. and M.I. reviewed the clinical presentations and collected patients. C.B. discovered the initial linkage. E.B., J. Hartley and C.J. undertook mutation screening. J.L.T. and M.K. conducted zebrafish work, and M.T. supervised it. S.R. and J. Hill conducted the immunohistochemistry. C.G.P. and M.W. performed the Tetrahymena thermophila experiments. P.J.S. planned the project from its inception and wrote the paper.
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Supplementary information
Supplementary Fig. 1
Conservation of amino acids affected by IFT80 alteration. (PDF 60 kb)
Supplementary Fig. 2
IFT80 depletion by RNAi. (PDF 95 kb)
Supplementary Fig. 3
Specificity and efficacy of ift80 morpholinos (PDF 66 kb)
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Beales, P., Bland, E., Tobin, J. et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat Genet 39, 727–729 (2007). https://doi.org/10.1038/ng2038
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DOI: https://doi.org/10.1038/ng2038
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