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A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus

A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus
A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus
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.
0340-6717
262-269
Mackay, D.J.G.
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Boonen, S.E.
d1c63e8f-4d38-4ff3-a6fd-f29db9a05e3b
Clayton-Smith, J.
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Goodship, J.
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Hahnemann, J.M.D.
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Kant, S.G.
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Njølstad, P.R.
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Robin, N.H.
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Robinson, D.O.
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Siebert, R.
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Shield, J.P.H.
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White, H.E.
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Temple, I.K.
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Mackay, D.J.G.
588a653e-9785-4a00-be71-4e547850ee4a
Boonen, S.E.
d1c63e8f-4d38-4ff3-a6fd-f29db9a05e3b
Clayton-Smith, J.
0d43489e-4266-4b0b-b7fa-bacc180062bd
Goodship, J.
e9a9e01a-a73f-42fa-81df-9354a8af731b
Hahnemann, J.M.D.
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Kant, S.G.
ec7029cd-ccec-4aad-a120-92b3496630c6
Njølstad, P.R.
9d13b32c-c44c-4bdd-9538-f206f9f950d3
Robin, N.H.
173329f0-8122-4eb8-bcc0-51b1244697a1
Robinson, D.O.
6b7e8cdc-b9c4-4ecf-a344-1bf0ae990f8a
Siebert, R.
4297324b-08e2-4ed7-8f63-43a4b18eae1b
Shield, J.P.H.
7e45e9e5-0a51-4086-87dc-8d4e2da7e5c8
White, H.E.
2181c0b9-fc3b-407e-95eb-3510524603e5
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226

Mackay, D.J.G., 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. and Temple, I.K. (2006) A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. Human Genetics, 120 (2), 262-269. (doi:10.1007/s00439-006-0205-2).

Record type: Article

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.

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Published date: September 2006
Organisations: Human Genetics, Medicine

Identifiers

Local EPrints ID: 44327
URI: http://eprints.soton.ac.uk/id/eprint/44327
ISSN: 0340-6717
PURE UUID: bd5e3a98-9b2c-48e0-a550-cd1527d32aeb
ORCID for D.J.G. Mackay: ORCID iD orcid.org/0000-0003-3088-4401
ORCID for I.K. Temple: ORCID iD orcid.org/0000-0002-6045-1781

Catalogue record

Date deposited: 26 Feb 2007
Last modified: 03 Dec 2019 01:56

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Contributors

Author: D.J.G. Mackay ORCID iD
Author: S.E. Boonen
Author: J. Clayton-Smith
Author: J. Goodship
Author: J.M.D. Hahnemann
Author: S.G. Kant
Author: P.R. Njølstad
Author: N.H. Robin
Author: D.O. Robinson
Author: R. Siebert
Author: J.P.H. Shield
Author: H.E. White
Author: I.K. Temple ORCID iD

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