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. 2021 Mar;99(3):425-429.
doi: 10.1111/cge.13890. Epub 2020 Nov 30.

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

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

Mattia Gentile et al. Clin Genet. 2021 Mar.

Abstract

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.

Keywords: CNV; congenital heart defects; human malformations; mTOR.

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