Imprinting mutation in the Beckwith-Wiedemann syndrome leads to biallelic IGF2 expression through an H19-independent pathway

Human Molecular Genetics
K W BrownW Reik

Abstract

The Beckwith-Wiedemann syndrome (BWS) is genetically linked to chromosome 11p15.5, and a variety of observations suggest that deregulation of imprinted genes in this region is causally involved in the pathogenesis of the disease. It has been shown that in some patients without cytogenetic abnormalities the otherwise repressed maternal copy of the insulin-like growth factor 2 (IGF2) gene is expressed, leading to biallelic expression of IGF2. In some of these cases, this is accompanied by repression and DNA methylation of the maternal (otherwise active) copy of the neighbouring H19 gene. Hence, it is attractive to think that mutations may interfere with some aspect of H19 imprinting, thus leading to an inactive maternal allele, and indirectly to activation of the maternal IGF2 allele as reported in mice with an H19 gene deletion. However, no mutations have been identified so far in these patients. The only known mutations associated with BWS are maternally transmitted translocations, which are clustered in two locations centrometric to IGF2. The first cluster is 200-400 kb from IGF2 and the second is several megabases away. Hence, genes located far from the translocation breakpoints are potentially deregulated by them. Here we pr...Continue Reading

Citations

Sep 25, 2001·The Journal of Pathology·M Paulsen, A C Ferguson-Smith
Aug 28, 1999·Molecular Biotechnology·J M Greally
Dec 19, 2012·Journal of Assisted Reproduction and Genetics·Deirdre Zander-FoxMichelle Lane
Aug 21, 2003·Lancet·Dian Donnai, Andrew P Read
Oct 16, 2003·Placenta·I CetinP Antonazzo
Dec 21, 2002·Trends in Genetics : TIG·Katharine L Arney
Aug 1, 1997·Trends in Genetics : TIG·W Reik, E R Maher
Apr 27, 2001·Toxicology Letters·P N SchofieldE R Maher
Jan 14, 2003·Seminars in Cell & Developmental Biology·Jörn Walter, Martina Paulsen
Jul 23, 2003·Human Molecular Genetics·Minjie DuPaul D Sadowski
Dec 9, 2009·Pigment Cell & Melanoma Research·Nan-Hyung KimAi-Young Lee
Nov 14, 1997·Journal of Medical Genetics·A SlavotinekD Donnai
May 1, 1997·Journal of Medical Genetics·D CatchpooleE R Maher
Jan 11, 2000·Journal of Medical Genetics·J R EngelE R Maher
Jan 1, 1997·Annual Review of Genetics·M S Bartolomei, S M Tilghman
Feb 17, 2000·The Journal of Clinical Investigation·E R Maher, W Reik
Feb 24, 2001·Genome Biology·J Peters
Mar 4, 2000·Environmental Health Perspectives·S K Murphy, R L Jirtle
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·K OkamotoA E Reeve
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·N J SmilinichM J Higgins
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·J M GabrielR D Nicholls
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·C SchwienbacherM Negrini
Jun 4, 1998·Current Opinion in Genetics & Development·W Reik, J Walter
Jul 10, 2010·The Journal of Molecular Diagnostics : JMD·Jochen K LennerzBarbara A Zehnbauer
Mar 11, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Hye Jeong LeeKinarm Ko
May 2, 2003·Annals of the New York Academy of Sciences·Maxwell P Lee
Apr 14, 2000·American Journal of Human Genetics·M AldersM Mannens
Aug 1, 1997·American Journal of Human Genetics·M P LeeA P Feinberg
Mar 18, 1999·The American Journal of Pathology·J G FallsR L Jirtle
Feb 26, 2016·Clinical Pharmacology and Therapeutics·M D BallantyneA H Baker
Sep 14, 2000·American Journal of Human Genetics·K Pfeifer
Aug 16, 2003·São Paulo Medical Journal = Revista Paulista De Medicina·Marcus Vinícius de Matos Gomes, Ester Silveira Ramos
Aug 12, 2009·Expert Opinion on Therapeutic Targets·Ilan BruchimHaim Werner
Jun 22, 2000·Human Mutation·E AlgarP Smith
Oct 23, 2001·Genesis : the Journal of Genetics and Development·S CroteauA K Naumova
Apr 24, 2002·Oncogene·Rosaria A M ScelfoMassimo Negrini

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.