Paternally Inherited IGF2 Mutation and Growth Restriction
Paternally Inherited IGF2 Mutation and Growth Restriction
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DOI：
10.1056/nejmoa1415227
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发表时间：
2015-07-23
影响因子：
158.5
通讯作者：
Eggermann, Thomas
中科院分区：
文献类型：
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作者：
Begemann, Matthias;Zirn, Birgit;Eggermann, Thomas
在人类中，IGF1或IGF1R突变导致宫内和出生后生长受限；然而，编码胰岛素样生长因子（IGF） II的IGF2突变的数据缺乏。我们报告了一个IGF2变异（c.191C -> A, p.Ser64Ter），在一个有四名生长受限成员的多代家族中具有致病性。该表型仅影响通过父系遗传了该变体的家庭成员，这一发现与IGF2的母系印记状态一致。受影响家庭成员的严重生长限制表明，IGF-II除了影响产前生长外，还影响产后生长。此外，受影响的家庭成员的畸形特征与缺乏IGF-II水平在引起银罗素综合征中的作用是一致的。
In humans, mutations in IGF1 or IGF1R cause intrauterine and postnatal growth restriction; however, data on mutations in IGF2, encoding insulin-like growth factor (IGF) II, are lacking. We report an IGF2 variant (c.191C -> A, p.Ser64Ter) with evidence of pathogenicity in a multigenerational family with four members who have growth restriction. The phenotype affects only family members who have inherited the variant through paternal transmission, a finding that is consistent with the maternal imprinting status of IGF2. The severe growth restriction in affected family members suggests that IGF-II affects postnatal growth in addition to prenatal growth. Furthermore, the dysmorphic features of affected family members are consistent with a role of deficient IGF-II levels in the cause of the Silver-Russell syndrome.