Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis (original) (raw)

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Acknowledgements

The authors thank M. Day, A. Damhuis and J. Garcia-Hurtado for technical assistance and R. Tearle (Complete Genomics), J. Tena and J.L. Skarmeta (Centro Andaluz de Biología del Desarrollo) for advice. J.F., S.E. and A.T.H. are supported by Wellcome Trust Senior Investigator awards. M.N.W. is supported by the Wellcome Trust as part of WT Biomedical Informatics Hub funding. E.D.F. is funded by the BOLD grant (European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement FP7-PEOPLE-ITN-2008 (Marie Curie Initial Training Networks, Biology of Liver and Pancreatic Development and Disease)). This work was supported by the National Institute for Health Research Exeter Clinical Research Facility through funding for S.E. and A.T.H. and general infrastructure and by the Ministerio de Economía y Competitividad (SAF2011-27086, PLE2009-0162 to J.F.). The views expressed here are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health, UK.

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Author notes

1. Michael N Weedon, Inês Cebola and Ann-Marie Patch: These authors contributed equally to this work.
2. Sian Ellard, Jorge Ferrer and Andrew T Hattersley: These authors jointly directed this work.

Authors and Affiliations

1. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
   Michael N Weedon, Ann-Marie Patch, Sarah E Flanagan, Elisa De Franco, Richard Caswell, Charles Shaw-Smith, Hana Lango Allen, Jayne A L Houghton, Anna Murray, Sian Ellard & Andrew T Hattersley
2. Genomic Regulation of Pancreatic Beta-Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
   Inês Cebola, Santiago A Rodríguez-Seguí & Jorge Ferrer
3. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas, Barcelona, Spain
   Inês Cebola, Santiago A Rodríguez-Seguí & Jorge Ferrer
4. Department of Medicine, Imperial College, London, UK
   Inês Cebola & Jorge Ferrer
5. Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute, Anne McLaren Laboratory for Regenerative Medicine, Cambridge, UK
   Candy H-H Cho & Ludovic Vallier
6. Seattle Children's Hospital Research Institute, Seattle, Washington, USA
   Christian L Roth
7. School of Biomedical Science, Waterloo Campus, King's College London, London, UK
   Rongrong Chen
8. London Centre for Paediatric Endocrinology and Metabolism, in partnership with the Great Ormond Street Hospital for Children National Health Service Trust, London, UK
   Khalid Hussain
9. Institute of Child Health, University College London, London, UK
   Khalid Hussain
10. Diabetes and Nutritional Sciences Division, Diabetes Research Group, School of Medicine, King's College London, London, UK
    Phil Marsh

Authors

1. Michael N Weedon
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2. Inês Cebola
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3. Ann-Marie Patch
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4. Sarah E Flanagan
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5. Elisa De Franco
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6. Richard Caswell
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7. Santiago A Rodríguez-Seguí
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8. Charles Shaw-Smith
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9. Candy H-H Cho
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10. Hana Lango Allen
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11. Jayne A L Houghton
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12. Christian L Roth
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13. Rongrong Chen
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14. Khalid Hussain
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15. Phil Marsh
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16. Ludovic Vallier
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17. Anna Murray
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18. Sian Ellard
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19. Jorge Ferrer
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20. Andrew T Hattersley
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Consortia

International Pancreatic Agenesis Consortium

Contributions

M.N.W., S.E., J.F. and A.T.H. designed the study. M.N.W., A.-M.P., J.A.L.H. and H.L.A. performed bioinformatic analyses. I.C., S.A.R.-S., C.H.-H.C., A.M., L.V. and J.F. performed functional studies. A.-M.P., J.A.L.H., E.D.F., R. Caswell, S.E.F. and S.E. performed Sanger sequencing or deletion analysis and interpreted the results. S.E.F., C.S.-S., K.H., C.L.R., R. Chen, P.M. and A.T.H. analyzed the clinical data. M.N.W., I.C., A.-M.P., S.E., J.F. and A.T.H. prepared the draft manuscript. All authors contributed to discussion of the results and to manuscript preparation.

Corresponding authors

Correspondence toJorge Ferrer or Andrew T Hattersley.

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The authors declare no competing financial interests.

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A full list of members and affiliations appears in the Supplementary Note.

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Weedon, M., Cebola, I., Patch, AM. et al. Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.Nat Genet 46, 61–64 (2014). https://doi.org/10.1038/ng.2826

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• Received: 12 July 2013
• Accepted: 16 October 2013
• Published: 10 November 2013
• Issue Date: January 2014
• DOI: https://doi.org/10.1038/ng.2826