Boonen SE

Clayton-Smith J

Goodship J

Hahnemann JMD

Kant SG

Mackay DJG

Njolstad PR

Robin NH

Robinson DO

Shield JPH

Siebert R

Temple IK

White HE

The expression of imprinted genes is mediated by allele-specific epigenetic modification of genomic DNA and chromatin, including parent of origin-specific DNA methylation. Dysregulation of these genes causes a range of disorders affecting pre- and post-natal growth and neurological function. We investigated a cohort of 12 patients with transient neonatal diabetes whose disease was caused by loss of maternal methylation at the TNDM locus. We found that six of these patients showed a spectrum of methylation loss, mosaic with respect to the extent of the methylation loss, the tissues affected and the genetic loci involved. Five maternally methylated loci were affected, while one maternally methylated and two paternally methylated loci were spared. These patients had higher birth weight and were more phenotypically diverse than other TNDM patients with different aetiologies, presumably reflecting the influence of dysregulation of multiple imprinted genes. We propose the existence of a maternal hypomethylation syndrome, and therefore suggest that any patient with methylation loss at one maternally-methylated locus may also manifest methylation loss at other loci, potentially complicating or even confounding the clinical presentation. \ua9 Springer-Verlag 2006

Newcastle University E-Prints

A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus

A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus

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