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Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57

Nature Genetics volume 40, pages 949–951 (2008)Cite this article

Abstract

We have previously described individuals presenting with transient neonatal diabetes and showing a variable pattern of DNA hypomethylation at imprinted loci throughout the genome. We now report mutations in ZFP57, which encodes a zinc-finger transcription factor expressed in early development, in seven pedigrees with a shared pattern of mosaic hypomethylation and a conserved range of clinical features. This is the first description of a heritable global imprinting disorder that is compatible with life.

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Figure 1: Sequence analysis of mutations in ZFP57.

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Acknowledgements

We thank E. Cross, C. Forristal, F. Houghton, C. Mattocks, A. Skinner and O. Wood for expert experimental assistance, N. Morton for calculating the degree of consanguinity of individuals in this study, the individuals with TND and their families for participation in the study and clinicians for their collaboration in this work. Funding for this study was from Diabetes UK (BDA:RD04/0002932 to D.J.G.M. and BDA:RD06/0003185 to J.L.A.C.).

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Authors and Affiliations

  1. Division of Human Genetics, University of Southampton, Southampton, SO16 6YD, UK

    Deborah J G Mackay, Jonathan L A Callaway, David O Robinson & I Karen Temple

  2. Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, SP2 8BJ, UK

    Deborah J G Mackay, Jonathan L A Callaway, Sophie M Marks & David O Robinson

  3. National Genetics Reference Laboratory Wessex, Salisbury, SP2 8BJ, UK

    Helen E White

  4. Department of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK

    Carlo L Acerini

  5. Genetic Counselling Clinic, Kennedy Center, DK-2600 Glostrup, Denmark

    Susanne E Boonen

  6. American Hospital, Nisantasi, Istanbul, 80200, Turkey

    Pinar Dayanikli

  7. Department of Medical Genetics, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK

    Helen V Firth

  8. Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK

    Judith A Goodship

  9. Department of Internal Medicine-Endocrinology, Maria Hospital Nord Limburg, 3900 Overpelt, Belgium

    Andreas P Haemers

  10. Medical Genetics Laboratory, Kennedy Center, DK-2600 Glostrup, Denmark

    Johanne M D Hahnemann

  11. Kinderkrankenhaus auf der Bult, Hannover, 30173, Germany

    Olga Kordonouri

  12. Children's Services, Northwick Park Hospital, Harrow, Middlesex, HA1 3UJ, UK

    Ahmed F Masoud

  13. Department of Clinical Genetics, National University Hospital Rigshospitalet, Copenhagen, 2100, Denmark

    Elsebet Oestergaard

  14. Department of Paediatrics, Cumberland Infirmary, Carlisle, CA2 7HY, Cumbria, UK

    John Storr

  15. Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, EX2 5DW, UK

    Sian Ellard & Andrew T Hattersley

  16. Academic Unit of Genetic Medicine, Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Southampton, SO16 5YA, UK

    I Karen Temple

Authors
  1. Deborah J G Mackay
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  2. Jonathan L A Callaway
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Contributions

D.J.G.M., J.L.A.C., S.M.M., H.E.W. and D.O.R. designed and performed genetic and epigenetic tests, and D.J.G.M. co-ordinated the molecular part of the study. C.L.A., S.E.B., P.D., H.V.F., J.A.G., A.P.H., J.M.D.H., O.K., A.F.M., E.O., J.S., S.E., A.T.H. and I.K.T. were involved in clinical characterization and referral of individuals with TND and the clinical study was coordinated by I.K.T.

Corresponding author

Correspondence to Deborah J G Mackay.

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Supplementary Methods, Supplementary Figures 1 and 2, Supplementary Tables 1–3 (PDF 926 kb)

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Mackay, D., Callaway, J., Marks, S. et al. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet 40, 949–951 (2008). https://doi.org/10.1038/ng.187

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