Molecular and clinical studies in 138 Japanese patients with Silver-Russell syndrome.
Molecular and clinical studies in 138 Japanese patients with Silver-Russell syndrome.
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DOI：
10.1371/journal.pone.0060105
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ogata T
中科院分区：
文献类型：
--
作者：
Fuke T;Mizuno S;Nagai T;Hasegawa T;Horikawa R;Miyoshi Y;Muroya K;Kondoh T;Numakura C;Sato S;Nakabayashi K;Tayama C;Hata K;Sano S;Matsubara K;Kagami M;Yamazawa K;Ogata T
最近的研究揭示了导致Silver-Russell综合征(SRS)的两个主要致病因素的相对频率和特征表型，即H19差异甲基化区域(DMR)和单亲母体二体7(UPD(7)MAT)的突变，以及H19-DMR突变中的多位点甲基化异常以及甲基化指数与身体和胎盘大小的正相关。此外，在少数特发性SRS患者中发现了罕见的基因组改变。在这里，我们对138名日本SRS患者进行了分子和临床表现，并对这些物质进行了检查。我们在病例1-43(组1)中发现H19-DMR半突变，在病例44-52(组2)中发现UPD(7)MAT，在病例53-138(组3)中既未发现H19-DMR半突变也未发现UPD(7)MAT。多位点分析显示，在第1组受检者中，有2.4%的受检者∼高度或低甲基化；尤其是在病例13中，发现了一种高度低甲基化的DMR。表型-表型分析显示，第1组新生儿出生时身长、体重明显小于第2组，出生枕额周长(OFC)保存较好，肢体不对称和指短畸形的发生率较高，言语发育迟缓的发生率较低。在第1组中，H19-DMR的甲基化指数与出生身长和体重、现在的身高和体重、胎盘重量呈正相关，但与出生和现在的胎盘重量无关。这一结果与以前报道的数据大体一致，尽管日本SRS患者的表型突变频率低于西欧SRS患者。此外，这些结果还为SRS的胎盘发育不良、低甲基化ARHI-DMR的临床表型以及特发性SRS的潜在致病因素提供了有用的信息。
Recent studies have revealed relative frequency and characteristic phenotype of two major causative factors for Silver-Russell syndrome (SRS), i.e. epimutation of the H19-differentially methylated region (DMR) and uniparental maternal disomy 7 (upd(7)mat), as well as multilocus methylation abnormalities and positive correlation between methylation index and body and placental sizes in H19-DMR epimutation. Furthermore, rare genomic alterations have been found in a few of patients with idiopathic SRS. Here, we performed molecular and clinical findings in 138 Japanese SRS patients, and examined these matters. We identified H19-DMR epimutation in cases 1–43 (group 1), upd(7)mat in cases 44–52 (group 2), and neither H19-DMR epimutation nor upd(7)mat in cases 53–138 (group 3). Multilocus analysis revealed hyper- or hypomethylated DMRs in 2.4% of examined DMRs in group 1; in particular, an extremely hypomethylated ARHI-DMR was identified in case 13. Oligonucleotide array comparative genomic hybridization identified a ∼3.86 Mb deletion at chromosome 17q24 in case 73. Epigenotype-phenotype analysis revealed that group 1 had more reduced birth length and weight, more preserved birth occipitofrontal circumference (OFC), more frequent body asymmetry and brachydactyly, and less frequent speech delay than group 2. The degree of placental hypoplasia was similar between the two groups. In group 1, the methylation index for the H19-DMR was positively correlated with birth length and weight, present height and weight, and placental weight, but with neither birth nor present OFC. The results are grossly consistent with the previously reported data, although the frequency of epimutations is lower in the Japanese SRS patients than in the Western European SRS patients. Furthermore, the results provide useful information regarding placental hypoplasia in SRS, clinical phenotypes of the hypomethylated ARHI-DMR, and underlying causative factors for idiopathic SRS.
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影响因子：
30.8
作者：
Gicquel, C;Rossignol, S;Le Bouc, Y
通讯作者：
Le Bouc, Y
影响因子：
64.8
作者：
HAO, Y;CRENSHAW, T;TYCKO, B
通讯作者：
TYCKO, B
影响因子：
64.8
作者：
Hark, AT;Schoenherr, CJ;Tilghman, SM
通讯作者：
Tilghman, SM
DOI：
10.1097/00005072-199612000-00011
发表时间：
1996-12-01
影响因子：
3.2
作者：
Albrecht, S;Waha, A;Pietsch, T
通讯作者：
Pietsch, T
DOI：
10.1016/j.beem.2010.06.005
发表时间：
2011-02-01
影响因子：
7.4
作者：
Binder, Gerhard;Begemann, Matthias;Kannenberg, Kai
通讯作者：
Kannenberg, Kai