The centromeric 11p15 imprinting centre is also involved in Silver–Russell syndrome

• Published in: Journal of medical genetics 2007-01, Vol.44 (1), p.59-63
• Main Authors: Schönherr, Nadine, Meyer, Esther, Roos, Andreas, Schmidt, Angela, Wollmann, Hartmut A, Eggermann, Thomas
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Automation; Beckwith-Wiedemann Syndrome - genetics; Beckwith–Wiedemann syndrome; Biological and medical sciences; BWS; Centromere - genetics; Child, Preschool; Chromosomes; Chromosomes, Human, Pair 11 - genetics; Classical genetics, quantitative genetics, hybrids; DNA Methylation; Epigenetics; Female; Fetal Growth Retardation; Fundamental and applied biological sciences. Psychology; Gene Duplication; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Genomic Imprinting; Growth Disorders - genetics; Human; Humans; ICR; imprinting centre region; Male; Medical genetics; Medical sciences; Microsatellite Repeats - genetics; Molecular and cellular biology; occipitofrontal circumference; OFC; Ostomy; Polymerase chain reaction; Pregnancy; Short Report; short tandem repeat; Silver–Russell syndrome; SRS; STR; Syndrome
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2006.044370

Silver–Russell syndrome (SRS) is a heterogeneous disorder characterised by severe intrauterine and postnatal growth retardation, limb and body asymmetry, a typical facial appearance and less common dysmorphisms. Recently, epimutations and maternal duplications affecting the short arm of chromosome 11 have been shown to have a crucial role in the aetiology of the disease. Disturbances in the same genomic region cause the overgrowth disorder Beckwith–Wiedemann syndrome (BWS). In BWS, mutations in the telomeric as well as in the centromeric imprinting centres (ICR1 and ICR2) in 11p15 can be observed. In SRS, methylation defects in the imprinted region in 11p15 were considered to be restricted to the telomeric ICR1. They can be detected in about 30% of patients. This article reports on the first patient with SRS with a cryptic duplication restricted to the centromeric ICR2 domain in 11p15. The maternally inherited duplication in this patient included a region of 0.76–1 Mbp and affected the genes regulated by the ICR2, among them CDKN1C and LIT1. This study provides evidence for a role for this imprinting centre in the aetiology of SRS and shows that SRS presents a picture genetically opposite to that of BWS.