title: Epigenetic deregulation of genomic imprinting in humans: causal mechanisms and clinical implications.
abstract: Mammalian genes controlled by genomic imprinting play important roles in development and diverse postnatal processes. A growing number of congenital disorders have been linked to genomic imprinting. Each of these is caused by perturbed gene expression at one principal imprinted domain. Some imprinting disorders, including the Prader-Willi and Angelman syndromes, are caused almost exclusively by genetic mutations. In several others, including the Beckwith-Wiedemann and Silver-Russell growth syndromes, and transient neonatal diabetes mellitus, imprinted expression is perturbed mostly by epigenetic alterations at 'imprinting control regions' and at other specific regulatory sequences. In a minority of these patients, DNA methylation is altered at multiple imprinted loci, suggesting that common trans-acting factors are affected. Here, we review the epimutations involved in congenital imprinting disorders and the associated clinical features. Trans-acting factors known to be causally involved are discussed and other trans-acting factors that are potentially implicated are also presented.
authors.affiliation: Institute of Molecular Genetics (IGMM), CNRS UMR-5535, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Girardot
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: David
authors.initials: D
authors.lastname: Llères
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities / Q000235:genetics*; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000235:genetics; D044127:Epigenesis, Genetic; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D056426:Genetic Loci; D015894:Genome, Human; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D015534:Trans-Activators