Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57.
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.
Mackay
Deborah J G
DJ
Division of Human Genetics, University of Southampton, Southampton SO16 6YD, UK. djgm@soton.ac.uk
Callaway
Jonathan L A
JL
Marks
Sophie M
SM
White
Helen E
HE
Acerini
Carlo L
CL
Boonen
Susanne E
SE
Dayanikli
Pinar
P
Firth
Helen V
HV
Goodship
Judith A
JA
Haemers
Andreas P
AP
Hahnemann
Johanne M D
JM
Kordonouri
Olga
O
Masoud
Ahmed F
AF
Oestergaard
Elsebet
E
Storr
John
J
Ellard
Sian
S
Hattersley
Andrew T
AT
Robinson
David O
DO
Temple
I Karen
IK
D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C531063:ZFP57 protein, human