No evidence of PEG1/MEST gene mutations in Silver-Russell syndrome patients
No evidence of PEG1/MEST gene mutations in Silver-Russell syndrome patients
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DOI：
10.1002/ajmg.10022
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发表时间：
2001-12-01
期刊：
影响因子：
--
通讯作者：
Ishino, F
中科院分区：
文献类型：
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作者：
Kobayashi, S;Uemura, H;Ishino, F
Silver-Russell 综合征 (SRS) 的特点是产前和产后生长迟缓并伴有形态异常。据报道，一些 SRS 患者存在母体单亲二倍体 7。 PEG1/MEST 是染色体 7q32 上的印记基因，仅从父本等位基因表达，是 SRS 的候选基因。为了阐明其生物学功能和在 SRS 中的作用，我们从不同角度筛选了 15 名 SRS 患者的 PEG1/MEST 异常。在SRS患者的淋巴细胞中，与正常样本相比，没有检测到PEG1/MEST的两种剪接变体（α和β）的异常表达模式。直接序列分析未能检测到PEG1/MEST a编码区有任何突变，并且包含预测启动子和高度保守的人/小鼠基因组区域的5'侧翼上游区域没有显着突变。 PEG1/MEST a 的 CpG 岛的差异甲基化模式通常保持不变，并产生与正常对照相同的模式，表明印记没有丢失。这些发现表明 PEG1/MEST 可以被排除在 SRS 的主要决定因素之外。 (C) 2001 Wiley-Liss, Inc.
Silver-Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a, candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (alpha and beta) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST a coding region, and there were no significant mutations in the 5'-flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST a were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. (C) 2001 Wiley-Liss, Inc.