Functional evidence of mTORβ splice variant involvement in the pathogenesis of congenital heart defects,Clinical Genetics

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Functional evidence of mTORβ splice variant involvement in the pathogenesis of congenital heart defects
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-11-24 , DOI: 10.1111/cge.13890
Mattia Gentile ₁ , Carlotta Ranieri ₂ , Daria C Loconte ₂ , Emanuela Ponzi ₁ , Romina Ficarella ₁ , Paolo Volpe ₃ , Gabriele Scalzo ₄ , Martina Lepore Signorile ₅ , Valentina Grossi ₅ , Angela Cordella ₆ , Giovanna Maria Ventola ₆ , Francesco C Susca ₁ , Antonella Turchiano ₂ , Cristiano Simone _{2,

5} , Nicoletta Resta ₂

Affiliation

mTOR dysregulation has been described in pathological conditions, such as cardiovascular and overgrowth disorders. Here we report on the first case of a patient with a complex congenital heart disease and an interstitial duplication in the short arm of chromosome 1, encompassing part of the mTOR gene. Our results suggest that an intragenic mTOR microduplication might play a role in the pathogenesis of non‐syndromic congenital heart defects (CHDs) due to an upregulation of mTOR/Rictor and consequently an increased phosphorylation of PI3K/AKT and MEK/ERK signaling pathways in patient‐derived amniocytes. This is the first report which shows a causative role of intragenic mTOR microduplication in the etiology of an isolated complex CHD.

中文翻译：

mTORβ剪接变异参与先天性心脏缺陷发病机制的功能证据

mTOR 失调已在病理状况中得到描述，例如心血管和过度生长障碍。在这里，我们报告了第一例患有复杂先天性心脏病和 1 号染色体短臂间质重复的患者，包括 mTOR 基因的一部分。我们的研究结果表明，由于 mTOR/Rictor 的上调以及患者体内 PI3K/AKT 和 MEK/ERK 信号通路的磷酸化增加，基因内 mTOR 微重复可能在非综合征型先天性心脏缺陷 (CHD) 的发病机制中发挥作用。衍生的羊水细胞。这是第一份报告，它显示了基因内 mTOR 微复制在孤立的复杂 CHD 的病因学中的致病作用。

更新日期：2020-11-24

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