Evidence against a major role of PEG1/MEST in Silver-Russell syndrome

被引:48
作者
Riesewijk, AM
Blagitko, N
Schinzel, AA
Hu, LD
Schulz, U
Hamel, BCJ
Ropers, HH
Kalscheuer, VM
机构
[1] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[2] Univ Nijmegen Hosp, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
[3] Univ Zurich, Inst Med Genet, CH-8006 Zurich, Switzerland
关键词
PEG1/MEST; Silver-Russell syndrome; uniparental disomy; imprinting;
D O I
10.1038/sj.ejhg.5200164
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:114 / 120
页数:7
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