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PMID: 16816970 Published · ppublish English Journal Article

A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus.

Human genetics ·Vol. 120 ·No. 2 ·2006-09-00 ·Pages 262-9

Mackay DJ, Boonen SE, Clayton-Smith J, Goodship J, Hahnemann JM, Kant SG, Njølstad PR, Robin NH, Robinson DO, Siebert R, Shield JP, White HE, Temple IK

Abstract

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.

MeSH Terms
Birth Weight Case-Control Studies Chromosomes, Human, Pair 6 Cohort Studies DNA Methylation Diabetes Mellitus/genetics Fathers Female Genomic Imprinting Humans Infant Infant, Newborn Male Mothers
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Mackay D J G
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, SP2 8BJ, UK.
Boonen S E
Clayton-Smith J
Goodship J
Hahnemann J M D
Kant S G
Njølstad P R
Robin N H
Robinson D O
Siebert R
Shield J P H
White H E
Temple I K
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Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
0340-6717
DOI
10.1007/s00439-006-0205-2
Published
2006-09-00
Epub
2006-00-01
Pages
262-9
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
External Links
PubMed source DOI: 10.1007/s00439-006-0205-2 View journal details
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