Severe Intrauterine Growth Retardation and Atypical Diabetes Associated with a Translocation Breakpoint Disrupting Regulation of the Insulin-Like Growth Factor 2 Gene

• DOI: 10.1210/jc.2008-0819
• Publication Date: 2008-08-27T00:44:41Z
• Authors: R. Murphy; J. Baptista; J. Holly; A. M. Umpleby; S. Ellard; L. W. Harries; J. Crolla; T. Cundy; A. T. Hattersley
• Keywords: Genomic Imprinting

Context: IGF-II is an imprinted gene (predominantly transcribed from the paternally inherited allele), which has important role in fetal growth mice. IGF2 expression regulated by a complex system of enhancers and promoters that determine tissue-specific development-specific transcription. In mice, are located up to 260 kb telomeric gene. The humans unclear. Objective: A woman short adult stature (1.46 m, −3 sd score) born with severe intrauterine retardation (1.25 kg at term, −5.4 atypical diabetes diagnosed age 23 yr had balanced chromosomal translocation t(1;11) (p36.22; p15.5). We hypothesized her phenotype resulted disruption derived because daughter who identical normal birth weight. Design: Both break points were identified using fluorescent situ hybridization. Sequence, methylation, was examined. Hyperinsulinemic, euglycemic clamp glucose tracers magnetic resonance imaging thorax, abdomen, pelvis performed. Results: 11p15.5 point mapped 184 Microsatellite markers confirmed paternal origin this chromosome. sequence methylation normal. reduced lymphoblasts. Clamp studies showed marked hepatic total insulin resistance. Massive excess sc fat seen on despite slim body mass index (21.1 kg/m2). Conclusions: upstream gene, separating it some enhancers, mesoderm-derived tissues causing retardation, stature, lactation failure, resistance altered distribution.