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Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE et al.. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet 40: 949-951

Division of Human Genetics, University of Southampton, Southampton SO16 6YD, UK.
Nature Genetics (Impact Factor: 29.65). 08/2008; 40(8):949-51. DOI: 10.1038/ng.187
Source: PubMed

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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    • "Intriguingly, human ZFP57 functionally replaces mouse Zfp57 in embryonic stem cells and mutation in human ZFP57 affect DNA methylation at a subset of imprinted loci in individuals suffering transient neonatal diabetes (Mackay et al., 2008; Takikawa et al., 2013). Altogether these studies suggested a conserved role for Zfp57 in the maintenance of DNA methylation pattern at imprinted loci in mammals, despite clear differences in early embryonic developmental processes. "
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    • "However, STELLA's global binding and protection of the whole maternal genome from active demethylation makes it an unlikely candidate for DNA methylation maintenance at specific loci. ZFP57, a Krueppel-associated box (KRAB) domain zinc finger protein, has also been associated with imprinting maintenance (Fig. 4C; Li et al. 2008; Mackay et al. 2008). "
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    • "Our findings are consistent with the hypothesis put forward by Fernandez-Rebollo et al. (2010) that PHP-1b is an autosomal recessive genetic disorder in some patients. The initial discovery of maternal hypomethylation syndrome led to the identification of mutations in the ZFP57 and NLRP2 genes in patients with TNDM and BWS, respectively, presenting multilocus imprinting defects [Mackay et al., 2008; Meyer et al., 2009]. Court et al. (2013) and Perez-Nanclares et al. (2012) failed to identify mutations in Figure 4. PTH and TSH resistance in patients with Spor-PHP-1b, including the patients with multilocus imprinting defects. "
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