Balanced Translocation t(3;12) Disrupting HMGA2 and NAALADL2 Genes in Twins With Silver-Russell Syndrome and Intellectual Disability.

Abstract

Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction. Most cases are caused by an imprinting error either with hypomethylation of the Imprinted Control Region 1 at 11p15.5, or maternal uniparental disomy of chromosome 7. Approximately 40% of the cases have unknown etiology, thus distinct mechanisms have been described in association with the syndrome. Here, we present a case of monozygotic twin sisters with a clinical diagnosis of SRS, mild intellectual disability and epilepsy who carry a balanced translocation between chromosomes 3 and 12 that interrupts the NAALADL2 and HMGA2 genes, respectively. Disruption of HMGA2, a gene previously described as causative of SRS, confirms the initial diagnosis. NAALADL2 gene has been recently proposed as a candidate for intellectual disability and could partially contribute to our patient's phenotype.