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

  • Nat Genet. 2008 Aug;40(8):949-51. doi: 10.1038/ng.187.
Deborah J G Mackay  1 ,  Jonathan L A Callaway ,  Sophie M Marks ,  Helen E White ,  Carlo L Acerini ,  Susanne E Boonen ,  Pinar Dayanikli ,  Helen V Firth ,  Judith A Goodship ,  Andreas P Haemers ,  Johanne M D Hahnemann ,  Olga Kordonouri ,  Ahmed F Masoud ,  Elsebet Oestergaard ,  John Storr ,  Sian Ellard ,  Andrew T Hattersley ,  David O Robinson ,  I Karen Temple
Affiliations
  • 1. Division of Human Genetics, University of Southampton, Southampton SO16 6YD, UK. [email protected]
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.