Referenced in: none

Automatically associated channels: Kv7.1

Title: Microduplication of the ICR2 domain at chromosome 11p15 and familial Silver-Russell syndrome.

Authors: Adriano Bonaldi, Juliana F Mazzeu, Silvia S Costa, Rachel S Honjo, Débora R Bertola, Lilian M J Albano, Isabel M Furquim, Chong A Kim, Angela M Vianna-Morgante

Journal, date & volume: Am. J. Med. Genet. A, 2011 Oct , 155A, 2479-83

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21910219

Abstract
Silver-Russell syndrome (SRS) is characterized by severe intrauterine and postnatal growth retardation in association with a typical small triangular face and other variable features. Genetic and epigenetic disturbances are detected in about 50% of the patients. Most frequently, SRS is caused by altered gene expression on chromosome 11p15 due to hypomethylation of the telomeric imprinting center (ICR1) that is present in at least 40% of the patients. Maternally inherited duplications encompassing ICR1 and ICR2 domains at 11p15 were found in a few patients, and a microduplication restricted to ICR2 was described in a single SRS child. We report on a microduplication of the ICR2 domain encompassing the KCNQ1, KCNQ1OT1, and CDKN1C genes in a three-generation family: there were four instances of paternal transmissions of the microduplication from a single male uniformly resulting in normal offspring, and five maternal transmissions, via two clinically normal sisters, with all the children exhibiting SRS. This report provides confirmatory evidence that a microduplication restricted to the ICR2 domain results in SRS when maternally transmitted.