Riesewijk A M, Blagitko N, Schinzel A A, Hu L, Schulz U, Hamel B C, Ropers H H, Kalscheuer V M
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
Eur J Hum Genet. 1998 Mar-Apr;6(2):114-20. doi: 10.1038/sj.ejhg.5200164.
Silver-Russell syndrome (SRS) is a heterogeneous disorder characterised by interauterine and postnatal growth retardation, with or without additional dysmorphic features. Most cases are sporadic but a few familial cases have been described. A subset of patients exhibit maternal uniparental disomy for chromosome 7 (mUPD7) strongly suggesting that genomic imprinting plays a role in the aetiology of the disease. We and others have recently characterised the human PEG1/MEST gene, the first imprinted gene known to be located on chromosome 7. Although the function of PEG1/MEST is unknown, the paternal-specific expression of this gene and its location at 7q32, render it a promising candidate for SRS. As a prerequisite for mutation screening in 49 patients with SRS and 9 with primordial growth retardation (PGR), we determined the complete genomic structure of the PEG1/MEST gene which consists of 12 exons. Apart from one silent mutation and two novel polymorphisms, nucleotide changes were not detected in any of these patients. Moreover, methylation patterns of the 5' region of PEG1/MEST were found to be normal in 35 SRS and 9 PGR patients and different from the pattern seen in patients with mUPD7. These findings strongly argue against a role of PEG1/MEST in the majority of Silver-Russell syndrome cases.
Silver-Russell综合征（SRS）是一种异质性疾病，其特征为宫内和出生后生长迟缓，伴有或不伴有其他畸形特征。大多数病例为散发性，但也有少数家族性病例的报道。一部分患者表现出7号染色体的母源单亲二倍体（mUPD7），这强烈提示基因组印记在该疾病的病因学中起作用。我们和其他人最近对人类PEG1/MEST基因进行了特征描述，这是已知位于7号染色体上的首个印记基因。尽管PEG1/MEST的功能尚不清楚，但该基因的父源特异性表达及其位于7q32的位置，使其成为SRS的一个有希望的候选基因。作为对49例SRS患者和9例原发性生长迟缓（PGR）患者进行突变筛查的前提，我们确定了由12个外显子组成的PEG1/MEST基因的完整基因组结构。除了一个沉默突变和两个新的多态性外，在这些患者中均未检测到核苷酸变化。此外，在35例SRS患者和9例PGR患者中发现PEG1/MEST 5'区域的甲基化模式正常，与mUPD7患者所见模式不同。这些发现有力地反驳了PEG1/MEST在大多数Silver-Russell综合征病例中的作用。
