Bruce Lefroy Centre, Murdoch Children's Research Institute, Parkville, 3052, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, 3052, Australia.
Ann Clin Transl Neurol. 2021 Feb;8(2):485-490. doi: 10.1002/acn3.51286. Epub 2021 Jan 12.
Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are related malformations with shared etiologies. We report three patients with a spectrum of cortical malformations associated with pathogenic brain-specific somatic Ras homolog enriched in brain (RHEB) variants. The somatic variant load directly correlated with the size of the malformation, with upregulated mTOR activity confirmed in dysplastic tissues. Laser capture microdissection showed enrichment of RHEB variants in dysmorphic neurons and balloon cells. Our findings support the role of RHEB in a spectrum of cortical malformations confirming that FCD and HME represent a disease continuum, with the extent of dysplastic brain directly correlated with the somatic variant load.
局灶性皮质发育不良（FCD）和大脑半球巨脑畸形（HME）是具有共同病因的相关畸形。我们报告了三例与脑特异性 Ras 同源物富集在脑（RHEB）变异体相关的皮质畸形综合征患者。体细胞变异负荷与畸形的大小直接相关，在发育不良组织中证实 mTOR 活性上调。激光捕获显微切割显示 RHEB 变异在畸形神经元和气球细胞中富集。我们的研究结果支持 RHEB 在一系列皮质畸形中的作用，证实 FCD 和 HME 代表一种疾病连续体，畸形脑的程度与体细胞变异负荷直接相关。
