Epigenetic Analysis of the IGF2/H19 locus in the NESTEGGG Small for Gestational Age Population

在低出生体重儿中，有一个亚群具有某些临床特征，被定义为Silver-Russell综合征。最近在其他地方的研究表明，在一定比例的SRS患者中，IGF-2基因的DNA特异性修饰存在异常。这种所谓的“表观遗传”修饰导致IGF-2生长因子的产生减少，从而为该综合征提供了一个解释。除了这项工作之外，内分泌中心还领导收集了大约1500个家庭，这些家庭有一个或多个孩子出生时体重偏低和/或儿童发育迟缓(筑巢研究)。这位研究员将调查SRS和Non-SRS患者中IGF-2基因表观遗传学异常的频率，并进一步检查IGF-2产生或作用减少的其他原因是否导致这种综合征，或总体上导致低出生体重。

Amongst low birth weight babies there is a subgroup with certain clinical features that are defined as Silver-Russell syndrome. Recent work elsewhere has shown there to be abnormalities in specific modifications to the DNA in the IGF-2 gene in a proportion of SRS patients. This so-called ‘epigenetic‘ modification results in reduced production of the IGF-2 growth factor which thus provides an explanation for the syndrome. Independently of this work the Endocrine Centre has led the collection of ~1500 families with one or more children born with low birth weight and/or failure of childhood growth (the NESTEGG study). The Fellow will investigate the frequency of epigenetic abnormalities of the IGF-2 gene in SRS and non-SRS patients in NESTEGG, and will further examine whether other causes of reduced production or action of IGF-2 contribute to this syndrome, or to low birth weight in general.