Genetic variation affecting DNA methylation and the human imprinting disorder, Beckwith-Wiedemann syndrome

Clinical Epigenetics
Vinod DagarElizabeth Algar

Abstract

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with a population frequency of approximately 1 in 10,000. The most common epigenetic defect in BWS is a loss of methylation (LOM) at the 11p15.5 imprinting centre, KCNQ1OT1 TSS-DMR, and affects 50% of cases. We hypothesised that genetic factors linked to folate metabolism may play a role in BWS predisposition via effects on methylation maintenance at KCNQ1OT1 TSS-DMR. Single nucleotide variants (SNVs) in the folate pathway affecting methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR), cystathionine beta-synthase (CBS) and methionine adenosyltransferase (MAT1A) were examined in 55 BWS patients with KCNQ1OT1 TSS-DMR LOM and in 100 unaffected cases. MTHFR rs1801133: C>T was more prevalent in BWS with KCNQ1OT1 TSS-DMR LOM (p < 0.017); however, the relationship was not significant when the Bonferroni correction for multiple testing was applied (significance, p = 0.0036). None of the remaining 13 SNVs were significantly different in the two populations tested. The DNMT1 locus was screened in 53 BWS cases, and three rare missense variants were identified in each of three patients: r...Continue Reading

References

Jan 1, 1996·Journal of Inherited Metabolic Disease·R Rozen
Nov 26, 1998·The Journal of Biological Chemistry·F GaudetR Jaenisch
May 3, 2000·American Journal of Epidemiology·L D Botto, Q Yang
Dec 14, 2001·Proceedings of the National Academy of Sciences of the United States of America·K YamadaR G Matthews
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Simonetta FrisoJacob Selhub
Sep 14, 2002·Journal of Inherited Metabolic Disease·H L LevyJ P Kraus
Oct 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Feng Ding, J Richard Chaillet
Nov 20, 2002·American Journal of Human Genetics·Michael R DeBaunAndrew P Feinberg
Jan 15, 2003·Journal of Medical Genetics·E R MaherM M Hawkins
Aug 23, 2006·Human Reproduction·A SatoT Arima
Aug 4, 2007·Science·Magnolia BostickSteven E Jacobsen
Nov 23, 2007·American Journal of Medical Genetics. Part a·Meredith WilsonElizabeth Algar
Jan 9, 2009·Nucleic Acids Research·Carina Frauer, Heinrich Leonhardt
Feb 10, 2009·Fertility and Sterility·Somjate ManipalviratnJames Segars
Jun 25, 2009·European Journal of Human Genetics : EJHG·Rosanna WeksbergJ Bruce Beckwith
Nov 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ewa BorowczykJ Richard Chaillet
Feb 5, 2011·Nature Protocols·Geraldine M ClarkeKrina T Zondervan
May 3, 2011·Nature Genetics·Christopher J KleinPeter J Dyck
Jul 10, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Lin RigbyElizabeth Algar
Nov 22, 2014·Nucleic Acids Research·Aron Marchler-BauerStephen H Bryant
Jun 14, 2015·Journal of Molecular Biology·Zhi-Min ZhangJikui Song
Sep 2, 2015·Nature Communications·Louise E DochertyDeborah J G Mackay
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Jul 16, 2016·American Journal of Medical Genetics. Part a·Saskia M MaasRaoul C Hennekam

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Citations

Feb 10, 2019·Biological Trace Element Research·Qiaojian ZhangShiwen Xu
Jan 17, 2019·Nature Reviews. Genetics·David MonkAndrea Riccio

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Datasets Mentioned

BETA
3027874

Methods Mentioned

BETA
PCR
flow
FCS
confocal microscopy
ELISA
pull-down

Software Mentioned

Clinvar
EXAc
Mutation Taster Variant Interpretation
PyroMark Q24
Mutation Surveyor
HGVS
GraphPad

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Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.

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