Bachmann Nadine, Spengler Sabrina, Binder Gerhard, Eggermann Thomas
Institute of Human Genetics, Technical University, Pauwelsstrasse 30, Aachen, Germany.
Eur J Med Genet. 2010 Jan-Feb;53(1):23-4. doi: 10.1016/j.ejmg.2009.12.002. Epub 2009 Dec 16.
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 ( approximately 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.
Silver-Russell综合征（SRS）是一种散发性、异质性疾病，主要与宫内和出生后生长发育迟缓有关。SRS患者中最常见的已知异常是11p15印记控制区1（ICR1）的低甲基化（约38%）。迄今为止，导致这种印记缺陷的基本机制尚不清楚。基于最近的研究发现，小鼠中甲基化CpG结合蛋白3（Mbd3）水平降低会导致ICR1发生特异性低甲基化，并导致胚胎体积变小，我们推测人类MBD3基因的基因组序列突变可能导致SRS。我们对20例ICR1低甲基化的SRS患者进行了MBD3突变分析，但在编码区未检测到任何致病变异。因此，我们认为MBD3的基因组突变与ICR1低甲基化的病因无关，因此与SRS也无关。
