Cytrynbaum, Cheryl, Chong, Karen, Hannig, Vickie, Choufani, Sanaa, Shuman, Cheryl, Steele, Leslie, Morgan, Thomas, Scherer, Stephen W, Stavropoulos, Dimitri J, Basran, Raveen K and Weksberg, Rosanna (2016) Genomic imbalance in the centromeric 11p15 imprinting center in three families: Further evidence of a role for IC2 as a cause of Russell-Silver syndrome. American journal of medical genetics. Part A, 170 (10). pp. 2731-2739. ISSN 1552-4833

Abstract

Russell-Silver syndrome is a heterogeneous disorder characterized by intrauterine growth retardation, postnatal growth deficiency, characteristic facial appearance, and other variable features. Genetic and epigenetic alterations are identified in about 60% of individuals with Russell-Silver syndrome. Most frequently, Russell-Silver syndrome is caused by altered gene expression on chromosome 11p15 due to loss of methylation at the telomeric imprinting center. To date there have been a handful of isolated clinical reports implicating the centromeric imprinting center 2 in the etiology of Russell-Silver syndrome. Here we report three new families with genomic imbalances, involving imprinting center 2 resulting in gain of methylation at this center and a Russell-Silver syndrome phenotype, including two families with a maternally inherited microduplication and the first pediatric patient with a paternally derived microdeletion. The findings in our families provide additional evidence of a role for imprinting center 2 in the etiology of Russell-Silver syndrome and suggest that imprinting center 2 imprinting abnormalities may be a more common cause of Russell-Silver syndrome than previously recognized. Furthermore, our findings together with previous clinical reports of genomic imbalances involving imprinting center 2 serve to underscore the complexity of the epigenetic regulation of the 11p15 region making it challenging to predict phenotype on the basis of genotype alone. © 2016 Wiley Periodicals, Inc.

Item Type:	Article
Date Deposited:	04 Oct 2016 00:45
Last Modified:	04 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/31108