Toggle Main Menu Toggle Search

Open Access padlockePrints

A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus

Lookup NU author(s): Professor Judith Goodship


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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. © Springer-Verlag 2006.

Publication metadata

Author(s): Mackay DJG, Boonen SE, Clayton-Smith J, Goodship J, Hahnemann JMD, Kant SG, Njolstad PR, Robin NH, Robinson DO, Siebert R, Shield JPH, White HE, Temple IK

Publication type: Article

Publication status: Published

Journal: Human Genetics

Year: 2006

Volume: 120

Issue: 2

Pages: 262-269

ISSN (print): 0340-6717

ISSN (electronic): 1432-1203

Publisher: Springer Berlin


DOI: 10.1007/s00439-006-0205-2


Altmetrics provided by Altmetric