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Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci

Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci
Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci
This study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell–Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). Thirty seven percent (37%) (29 of 79) of samples were shown to have a methylation abnormality. The commonest finding was a loss of methylation at H19 (23 of 29), as previously reported in Russell–Silver Syndrome. In addition, four of these patients had methylation anomalies at other loci, of whom two showed hypomethylation of multiple imprinted loci, and two showed a complete gain of methylation at IGF2R. This latter finding was also present in five other patients who did not have demonstrable changes at H19. In total, 7 of 79 patients showed a gain of methylation at IGF2R and this was significantly different from a normal control population of 267 individuals (P=0.002). This study in patients with growth restriction shows the importance of widening the epigenetic investigation to include multiple imprinted loci and highlights potential involvement of the IGF2R locus
growth restriction, russell–silver syndrome, 11p15 epimutation, H19, IGF2R, hypomethylation of imprinted loci
1018-4813
648-655
Turner, Claire Louise
a1c55c23-89b8-47fe-9b90-86e87749473b
Mackay, Deborah M.
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Callaway, Jonathan L.A.
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Docherty, Louise E.
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Poole, Rebecca L.
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Bullman, Hilary
dd727e9a-42ba-48d5-a7bc-499ff5c5e9f2
Lever, Margaret
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Castle, Bruce M.
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Kivuva, Emma C.
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Turnpenny, Peter D.
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Mehta, Sarju G.
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Mansour, Sahar
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Wakeling, Emma L.
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Mathew, Verghese
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Madden, Jackie
0771e352-d432-41ea-8a7e-4704c1efca46
Davies, Justin H.
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Temple, I. Karen
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Turner, Claire Louise
a1c55c23-89b8-47fe-9b90-86e87749473b
Mackay, Deborah M.
588a653e-9785-4a00-be71-4e547850ee4a
Callaway, Jonathan L.A.
52ebaa48-83d6-4270-ad74-666f70264f29
Docherty, Louise E.
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Poole, Rebecca L.
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Bullman, Hilary
dd727e9a-42ba-48d5-a7bc-499ff5c5e9f2
Lever, Margaret
4d112693-a8b5-46d9-8759-29e3677f31d6
Castle, Bruce M.
cc80c50c-dacd-4092-8d0b-76fde2f77563
Kivuva, Emma C.
75dbcf02-6241-4ee2-b10e-248e6506da70
Turnpenny, Peter D.
167584d7-ed26-49e9-bdf4-f441b7f1e7be
Mehta, Sarju G.
485e0fbf-763e-46d7-807e-2e43f2b6e183
Mansour, Sahar
fcece354-b435-46fb-8acf-184dad0ed4c2
Wakeling, Emma L.
8ae66ff5-bca4-4c71-8f71-7157329bebda
Mathew, Verghese
94a7ef9d-1de6-4420-aa44-d94ab1c13986
Madden, Jackie
0771e352-d432-41ea-8a7e-4704c1efca46
Davies, Justin H.
9f18fcad-f488-4c72-ac23-c154995443a9
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226

Turner, Claire Louise, Mackay, Deborah M., Callaway, Jonathan L.A., Docherty, Louise E., Poole, Rebecca L., Bullman, Hilary, Lever, Margaret, Castle, Bruce M., Kivuva, Emma C., Turnpenny, Peter D., Mehta, Sarju G., Mansour, Sahar, Wakeling, Emma L., Mathew, Verghese, Madden, Jackie, Davies, Justin H. and Temple, I. Karen (2010) Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci. European Journal of Human Genetics, 18 (6), 648-655. (doi:10.1038/ejhg.2009.246).

Record type: Article

Abstract

This study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell–Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). Thirty seven percent (37%) (29 of 79) of samples were shown to have a methylation abnormality. The commonest finding was a loss of methylation at H19 (23 of 29), as previously reported in Russell–Silver Syndrome. In addition, four of these patients had methylation anomalies at other loci, of whom two showed hypomethylation of multiple imprinted loci, and two showed a complete gain of methylation at IGF2R. This latter finding was also present in five other patients who did not have demonstrable changes at H19. In total, 7 of 79 patients showed a gain of methylation at IGF2R and this was significantly different from a normal control population of 267 individuals (P=0.002). This study in patients with growth restriction shows the importance of widening the epigenetic investigation to include multiple imprinted loci and highlights potential involvement of the IGF2R locus

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More information

Accepted/In Press date: 27 January 2010
Published date: July 2010
Keywords: growth restriction, russell–silver syndrome, 11p15 epimutation, H19, IGF2R, hypomethylation of imprinted loci
Organisations: Human Genetics, Dev Origins of Health & Disease

Identifiers

Local EPrints ID: 72192
URI: http://eprints.soton.ac.uk/id/eprint/72192
ISSN: 1018-4813
PURE UUID: accd86ba-c256-44d8-a94c-ed9d21ca6a9a
ORCID for Deborah M. Mackay: ORCID iD orcid.org/0000-0003-3088-4401
ORCID for I. Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781

Catalogue record

Date deposited: 29 Jan 2010
Last modified: 14 Mar 2024 02:42

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Contributors

Author: Claire Louise Turner
Author: Jonathan L.A. Callaway
Author: Louise E. Docherty
Author: Rebecca L. Poole
Author: Hilary Bullman
Author: Margaret Lever
Author: Bruce M. Castle
Author: Emma C. Kivuva
Author: Peter D. Turnpenny
Author: Sarju G. Mehta
Author: Sahar Mansour
Author: Emma L. Wakeling
Author: Verghese Mathew
Author: Jackie Madden
Author: I. Karen Temple ORCID iD

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