title: Adult phenotype of Russell-Silver syndrome: A molecular support for Barker-Brenner's theory.
abstract: Developmental Origins of Health and Disease theory stems from large-scale epidemiologic observation. The presumed mechanism for this hypothesis includes epigenetic changes; however, it remains to be elucidated if individuals with intrauterine growth retardation and epigenetic changes confirmed at the molecular level are indeed susceptible to adult-onset disease. Here we document three individuals with Russell-Silver syndrome, a prototypic condition caused by hypomethylation of the differently methylated imprinting center region 1 (ICR1) between the IGF2 and H19 loci on chromosome 11p15. At follow-up, the three patients developed adult-onset diseases such as obesity, hypertension, and diabetes mellitus in their early 20s. The presence of molecularly confirmed epigenetic changes in these patients provides a biological basis for Barker-Brenner's theory at an individual level.
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.|Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors: Toshiki
authors: T
authors: Takenouchi
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Midori
authors: M
authors: Awazu
authors: Institute of Human Genetics, RWTH Aachen, Germany.
authors: Thomas
authors: T
authors: Eggermann
authors: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors: Kenjiro
authors: K
authors: Kosaki
mesh_terms: D000328:Adult; D017668:Age of Onset; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000209:etiology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000473:pathology; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D009765:Obesity / Q000209:etiology* / Q000473:pathology; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics*; D056730:Silver-Russell Syndrome / Q000150:complications* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II
keywords: adult-onset diseases; developmental origins of health and disease; epigenetics; insulin-like growth factor 2; russell-silver syndrome