Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome
Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome
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DOI：
10.1038/ng1629
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发表时间：
2005-09-01
期刊：
影响因子：
30.8
通讯作者：
Le Bouc, Y
中科院分区：
文献类型：
--
作者：
Gicquel, C;Rossignol, S;Le Bouc, Y
银-罗素综合征（SRS，OMIM 180860）是一种先天性疾病，其特征是严重的宫内和出生后生长迟缓，畸形的面部特征和身体不对称。SRS是遗传异质性与母体单亲二体性相对于染色体7发生在类似的10%的受影响的个人。鉴于11 p15印迹区域在控制胎儿生长中的关键作用，我们假设11 p15基因的失调可能与综合征性宫内生长迟缓有关。我们确定了一个epimutation（去甲基化）在端粒印迹中心区ICR 1的11 p15区域在几个人与临床典型的SRS。这种表观遗传缺陷与H19的印记和双等位基因表达的松弛以及IGF 2的下调相关，并且可能是其原因。这些发现为SRS的发病机制提供了新的见解，并强烈提示除了7p11.2- p13和7 q31- qter的印迹区域之外，11 p15印迹区域也参与SRS。
Silver- Russell syndrome ( SRS, OMIM 180860) is a congenital disorder characterized by severe intrauterine and postnatal growth retardation, dysmorphic facial features and body asymmetry. SRS is genetically heterogenous with maternal uniparental disomy with respect to chromosome 7 occurring in similar to 10% of affected individuals. Given the crucial role of the 11p15 imprinted region in the control of fetal growth, we hypothesized that dysregulation of genes at 11p15 might be involved in syndromic intrauterine growth retardation. We identified an epimutation ( demethylation) in the telomeric imprinting center region ICR1 of the 11p15 region in several individuals with clinically typical SRS. This epigenetic defect is associated with, and probably responsible for, relaxation of imprinting and biallelic expression of H19 and downregulation of IGF2. These findings provide new insight into the pathogenesis of SRS and strongly suggest that the 11p15 imprinted region, in addition to those of 7p11.2- p13 and 7q31- qter, is involved in SRS.