MBD3 mutations are not responsible for ICR1 hypomethylation in Silver–Russell syndrome

Abstract

Silver–Russell syndrome (SRS) is a sporadic and heterogeneous disease that is mainly associated with intrauterine and postnatal growth retardation. The most frequent known aberration in SRS patients is a hypomethylation of the imprinting control region 1 (ICR1) in 11p15 (∼38%). Up to now the basic mechanisms leading to this imprinting defect are unknown. Based on the recent findings that a reduced level of the methyl-CpG binding protein 3 (Mbd3) in mice results in a specific hypomethylation of the ICR1 and in a smaller size of embryos we hypothesized that mutations in the genomic sequence of the human MBD3 gene might cause SRS. We carried out mutation analysis of MBD3 in 20 SRS patients with hypomethylation of the ICR1 but did not detect any pathogenic variant in the coding region. Thus we assume that genomic mutations of MBD3 are not relevant for the aetiology of the ICR1 hypomethylation and therefore for SRS.