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IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy

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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Figure 1: IFT80 mutations in JATD.
Figure 2: Expression and function analysis of Ift80.

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References

  1. Badano, J.L., Mitsuma, N., Beales, P.L. & Katsanis, N. Annu. Rev. Genomics Hum. Genet. 7, 125–148 (2006).

    Article  CAS  Google Scholar 

  2. Li, J.B. et al. Cell 117, 541–552 (2004).

    Article  CAS  Google Scholar 

  3. Efimenko, E. et al. Development 132, 1923–1934 (2005).

    Article  CAS  Google Scholar 

  4. Kunitomo, H., Uesugi, H., Kohara, Y. & Lino, Y. Genome Biol. 6, R17 (2005).

    Article  Google Scholar 

  5. Blacque, O.E. et al. Genes Dev. 18, 1630–1642 (2004).

    Article  CAS  Google Scholar 

  6. Ou, G. et al. Nature 436, 583–587 (2005).

    Article  CAS  Google Scholar 

  7. Rosenbaum, J.L. & Witman, G.B. Nat. Rev. Mol. Cell Biol. 3, 813–825 (2002).

    Article  CAS  Google Scholar 

  8. Collins, K. & Gorovsky, M.A. Curr. Biol. 15, R317–R318 (2005).

    Article  CAS  Google Scholar 

  9. Sun, Z. et al. Development 131, 4085–4093 (2004).

    Article  CAS  Google Scholar 

  10. Haycraft, C.J. et al. PLoS Genet. 1, e53 (2005).

    Article  Google Scholar 

  11. May, S.R. et al. Dev. Biol. 287, 378–389 (2005).

    Article  CAS  Google Scholar 

  12. Liu, A., Wang, B. & Niswander, L.A. Development 132, 3103–3111 (2005).

    Article  CAS  Google Scholar 

  13. Wada, N. et al. Development 132, 3977–3988 (2005).

    Article  CAS  Google Scholar 

  14. Haycraft, C.J. et al. Development 134, 307–316 (2007).

    Article  CAS  Google Scholar 

Download references

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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Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Peter J Scambler.

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The authors declare no competing financial interests.

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)

Supplementary Methods (PDF 50 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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