Department of Genetics and Cytogenetics, AP-HP, Institut du Cerveau et de la Moelle Epinière (ICM) - Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm U1127, CNRS UMR 7225, Paris, France.
Neuropathol Appl Neurobiol. 2018 Feb;44(1):6-17. doi: 10.1111/nan.12463.
Over the last decade, there has been increasing evidence that hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is a hallmark of malformations of cortical development such as focal cortical dysplasia (FCD) or hemimegalencephaly. The mTOR pathway governs protein and lipid synthesis, cell growth and proliferation as well as metabolism and autophagy. The molecular genetic aetiology of mTOR hyperactivation has only been recently clarified. This article will review the current and still evolving genetic advances in the elucidation of the molecular basis of FCD. Activating somatic mutations in the MTOR gene are to date the most frequent mutations found in FCD brain specimens.
在过去的十年中，越来越多的证据表明，雷帕霉素（mTOR）途径的过度激活是皮质发育畸形（如局灶性皮质发育不良或巨脑回畸形）的标志。mTOR 途径控制着蛋白质和脂质的合成、细胞的生长和增殖以及代谢和自噬。mTOR 过度激活的分子遗传病因学直到最近才被阐明。本文将回顾当前仍在不断发展的遗传进展，以阐明 FCD 的分子基础。迄今为止，在 FCD 脑标本中发现的最常见的突变是 MTOR 基因的激活性体细胞突变。
