KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes (original) (raw)

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References

1. Baker, K. & Beales, P.L. Making sense of cilia in disease: the human ciliopathies. Am. J. Med. Genet. C. Semin. Med. Genet. 151C, 281–295 (2009).
   Article CAS Google Scholar
2. Salonen, R., Herva, R. & Norio, R. The hydrolethalus syndrome: delineation of a “new,” lethal malformation syndrome based on 28 patients. Clin. Genet. 19, 321–330 (1981).
   Article CAS Google Scholar
3. Mee, L. et al. Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1. Hum. Mol. Genet. 14, 1475–1488 (2005).
   Article CAS Google Scholar
4. Dammermann, A. et al. The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation. Genes Dev. 23, 2046–2059 (2009).
   Article CAS Google Scholar
5. Schinzel, A. & Schmid, W. Hallux duplication, postaxial polydactyly, absence of the corpus callosum, severe mental retardation, and additional anomalies in two unrelated patients: a new syndrome. Am. J. Med. Genet. 6, 241–249 (1980).
   Article CAS Google Scholar
6. Schinzel, A. & Kaufmann, U. The acrocallosal syndrome in sisters. Clin. Genet. 30, 399–405 (1986).
   Article CAS Google Scholar
7. Robbins, D.J. et al. Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Cell 90, 225–234 (1997).
   Article CAS Google Scholar
8. Kalderon, D. Hedgehog signaling: Costal-2 bridges the transduction gap. Curr. Biol. 14, R67–R69 (2004).
   Article CAS Google Scholar
9. Cheung, H.O. et al. The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling. Sci. Signal. 2, ra29 (2009).
   Article Google Scholar
10. Endoh-Yamagami, S. et al. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr. Biol. 19, 1320–1326 (2009).
    Article CAS Google Scholar
11. Liem, K.F. Jr., He, M., Ocbina, P.J. & Anderson, K.V. Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling. Proc. Natl. Acad. Sci. USA 106, 13377–13382 (2009).
    Article CAS Google Scholar
12. Khanna, H. et al. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat. Genet. 41, 739–745 (2009).
    Article CAS Google Scholar
13. Leitch, C.C. et al. Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat. Genet. 40, 443–448 (2008).
    Article CAS Google Scholar
14. Zaghloul, N.A. et al. Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet-Biedl syndrome. Proc. Natl. Acad. Sci. USA 107, 10602–10607 (2010).
    Article CAS Google Scholar
15. Tay, S.Y., Ingham, P.W. & Roy, S. A homologue of the Drosophila kinesin-like protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo. Development 132, 625–634 (2005).
    Article CAS Google Scholar
16. Nasevicius, A. & Ekker, S.C. Effective targeted gene 'knockdown' in zebrafish. Nat. Genet. 26, 216–220 (2000).
    Article CAS Google Scholar
17. Wilson, C.W. et al. Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis. Nature 459, 98–102 (2009).
    Article CAS Google Scholar
18. Wolff, C., Roy, S. & Ingham, P.W. Multiple muscle cell identities induced by distinct levels and timing of hedgehog activity in the zebrafish embryo. Curr. Biol. 13, 1169–1181 (2003).
    Article CAS Google Scholar
19. Badano, J.L. et al. Dissection of epistasis in oligogenic Bardet-Biedl syndrome. Nature 439, 326–330 (2006).
    Article CAS Google Scholar
20. Davis, E.E. et al. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat. Genet. 43, 189–196 (2011).
    Article CAS Google Scholar
21. Patzke, S. et al. CSPP is a ciliary protein interacting with Nephrocystin 8 and required for cilia formation. Mol. Biol. Cell 21, 2555–2567 (2010).
    Article CAS Google Scholar
22. Delous, M. et al. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat. Genet. 39, 875–881 (2007).
    Article CAS Google Scholar
23. Valente, E.M. et al. Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat. Genet. 42, 619–625 (2010).
    Article CAS Google Scholar
24. Goetz, S.C. & Anderson, K.V. The primary cilium: a signalling centre during vertebrate development. Nat. Rev. Genet. 11, 331–344 (2010).
    Article CAS Google Scholar
25. Kim, J. et al. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature 464, 1048–1051 (2010).
    Article CAS Google Scholar
26. Monnier, V., Ho, K.S., Sanial, M., Scott, M.P. & Plessis, A. Hedgehog signal transduction proteins: contacts of the Fused kinase and Ci transcription factor with the kinesin-related protein Costal2. BMC Dev. Biol. 2, 4 (2002).
    Article Google Scholar
27. Martinelli, D.C. & Fan, C.M. Gas1 extends the range of Hedgehog action by facilitating its signaling. Genes Dev. 21, 1231–1243 (2007).
    Article CAS Google Scholar

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Acknowledgements

We are grateful to families and to the French Society of Fetal Pathology (SOFFOET) for participating in the study, to C. Dubourg, P. Wieacker, B. Leroy, N. Laurent, V. Fermeaux, S. Odent for fetuses' referral and to A. Schinzel and A. David for ACLS samples. We thank M. Zarhrate, A. Aguilar, N. Spasky and L. Besse for technical help. We thank N. Boddaert for helpful discussion. This work was supported by grants from ANR (FETALCILIOPATHIES number 07-MRAR-010-02 and FOETOCILPATH number BLAN-1122-01), E-RARE (Cranirare number 07-ERare-001-01) the Scientific and Technological Research Council of Turkey (TUBITAK, grant number 108S420 to N.A.A.), the US National Institutes of Health grant R01HD04260 from the National Institute of Child Health and Development (N.K.), R01DK072301 from the National Institute of Diabetes, Digestive and Kidney Disorders (N.K.) and the European Union (EU-SYSCILIA; E.E.D., N.K. and P.L.B.). A.P. was granted a fellowship from the Académie de Médecine. S.T. is supported by NIH 'Hereditary Basis of Neural Tube Defects' N° NS039818-07 to M. Speer. K.L.M.C. is supported by the Huygens Scholarship Programme and the Netherlands Organization for Scientific Research (NWO Toptalent-021.001.014). M.W. was a fellow of the Guggenheim Foundation and was supported by the March of Dimes Foundation (1-FY07-422). P.L.B. is a Wellcome Trust Senior Research Fellow. N.K. is a Distinguished George W. Brumley Professor.

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Author notes

1. Audrey Putoux and Sophie Thomas: These authors contributed equally to this work.

Authors and Affiliations

1. INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France
   Audrey Putoux, Sophie Thomas, Céline Gomes, Laura Fertitta, Arnold Munnich, Valérie Cormier-Daire, Stanislas Lyonnet, Férechté Encha-Razavi, Michel Vekemans & Tania Attié-Bitach
2. Université René Descartes, Paris, France
   Audrey Putoux, Sophie Thomas, Arnold Munnich, Valérie Cormier-Daire, Stanislas Lyonnet, Férechté Encha-Razavi, Michel Vekemans & Tania Attié-Bitach
3. Department of Human Genetics and Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
   Karlien L M Coene
4. Center for Human Disease Modeling, Duke University, Durham, North Carolina, USA
   Erica E Davis & Nicholas Katsanis
5. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA
   Erica E Davis
6. Department of Pediatrics, Pediatric Genetics Unit, Hacettepe University Medical Faculty, Ankara, Turkey
   Yasemin Alanay, Gulen Eda Utine & Koray Boduroglu
7. Department of Medical/Pediatric Genetics, Ondokuz Mayis University, Samsun, Turkey
   Gönül Ogur & Christopher L Bennett
8. Department of Medical Genetics, Gene Mapping Laboratory, Hacettepe University Medical Faculty, Ankara, Turkey
   Elif Uz & Nurten Ayse Akarsu
9. Service de Gynécologie-Obstétrique, Centre Hospitalier (CH) Sud Francilien, Evry, France
   Daniela Buzas & Luc Rigonnot
10. Service de Génétique et d'Embryologie Médicales, Hôpital Armand Trousseau, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
    Sophie Patrier, Nicole Joyé, Jean-Pierre Siffroi & Marie Gonzales
11. Département de Génétique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
    Nadia Elkhartoufi, Arnold Munnich, Valérie Cormier-Daire, Stanislas Lyonnet, Férechté Encha-Razavi, Michel Vekemans & Tania Attié-Bitach
12. Service d'Anatomie et Cytologie Pathologiques, CH Victor Dupouy, Argenteuil, France
    Marie-Hélène Saint Frison
13. Université Pierre et Marie Curie, Paris, France
    Nicole Joyé, Jean-Pierre Siffroi & Marie Gonzales
14. Genomic Core Facility, Imagine Fondation, Hôpital Necker-Enfants Malades, Paris, France
    Solenn Pruvost & Christine Bole-Feysot
15. Service de Bioinformatique, Université Paris Descartes, Paris, France
    Patrick Nitschke & Nicolas Cagnard
16. Service de Génétique, CHU de Dijon, Dijon, France
    Christel Thauvin-Robinet
17. Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Raoul Hennekam
18. Service de Génétique, Hôpital d'Angers, Angers, France
    Estelle Colin
19. CNRS UMR 8104, Institut Cochin, Université Paris Descartes, Paris, France
    Alain Schmitt
20. IFR 94, Faculté de Médecine Necker, Paris, France
    Nicolas Goudin
21. Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado, USA
    Mark Winey
22. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
    Nicholas Katsanis
23. Molecular Medicine Unit, University College London (UCL) Institute of Child Health, London, UK
    Philip L Beales

Authors

1. Audrey Putoux
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2. Sophie Thomas
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3. Karlien L M Coene
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4. Erica E Davis
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5. Yasemin Alanay
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6. Gönül Ogur
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7. Elif Uz
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8. Daniela Buzas
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9. Céline Gomes
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10. Sophie Patrier
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11. Christopher L Bennett
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12. Nadia Elkhartoufi
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13. Marie-Hélène Saint Frison
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14. Luc Rigonnot
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15. Nicole Joyé
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16. Solenn Pruvost
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17. Gulen Eda Utine
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18. Koray Boduroglu
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19. Patrick Nitschke
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20. Laura Fertitta
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21. Christel Thauvin-Robinet
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22. Arnold Munnich
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23. Valérie Cormier-Daire
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24. Raoul Hennekam
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25. Estelle Colin
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26. Nurten Ayse Akarsu
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27. Christine Bole-Feysot
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28. Nicolas Cagnard
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29. Alain Schmitt
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30. Nicolas Goudin
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31. Stanislas Lyonnet
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32. Férechté Encha-Razavi
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33. Jean-Pierre Siffroi
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34. Mark Winey
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35. Nicholas Katsanis
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36. Marie Gonzales
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37. Michel Vekemans
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38. Philip L Beales
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39. Tania Attié-Bitach
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Contributions

S. Patrier, M.-H.S.F., F.E.-R. and J.-P.S. performed the fetal examinations. N.J. did the fetal karyotyping. L.R. and M.G. referred the HLS family. D.B. did the ultrasound diagnosis. G.O., Y.A., G.E.U., K.B., R.H., P.L.B., C.T., V.C.-D. and E.C. referred subjects. C.L.B., M.W., K.C., N.A.A., C.B.-F., E.U. and P.N. performed the homozygosity mapping and LOD score calculation. C.G., N.E., L.F., K.L.M.C., M.W. and C.B.-F. performed linkage and sequence analyses. S. Pruvost and E.U. did the chip experiments. S.T. and N.C. performed the expression analysis. A.S. performed the electron microscopy. N.G. and A.P. performed the confocal microscopy and measurement of cilia length. E.E.D. and N.K. did the zebrafish experiments. A.M., S.L. and M.V. advised the work. T.A.-B. designed the study and wrote the manuscript.

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Correspondence toTania Attié-Bitach.

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The authors declare no competing financial interests.

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Putoux, A., Thomas, S., Coene, K. et al. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes.Nat Genet 43, 601–606 (2011). https://doi.org/10.1038/ng.826

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• Received: 19 July 2010
• Accepted: 08 April 2011
• Published: 08 May 2011
• Issue Date: June 2011
• DOI: https://doi.org/10.1038/ng.826