机构：[1]Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.医技科室病理科首都医科大学宣武医院[2]Clinical Research Center for Epilepsy, Xuanwu Hospital, Beijing, 100053, China.首都医科大学宣武医院[3]National Center for Neurological Disorders, Beijing, 100053, China.[4]Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.神经科系统神经外科功能神经外科首都医科大学宣武医院[5]Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.神经科系统神经外科功能神经外科首都医科大学宣武医院[6]Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.[7]Department of Neurobiology and Clinical Biobank, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.首都医科大学宣武医院[8]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.神经科系统神经内科首都医科大学宣武医院[9]Beijing Key Laboratory of Neuromodulation, Beijing, 100053, China.[10]Center of Epilepsy, Institute of Sleep and Consciousness Disorders, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100053, China.
Focal Cortical Dysplasia (FCD) is a major cause of drug-resistant paediatric epilepsy and is amenable to successful neurosurgical resection. FCD ILAE Type IIb is the most common FCD subtype, and brain somatic mutations affecting the mTOR pathway play a major pathogenic role. The aim of this study was to comprehensively describe the genotype-phenotype association of twenty patients with histopathologically confirmed FCDIIb using Next Generation Sequencing (NGS) of paired blood-brain samples METHODS: Clinical and neuropathological data were retrospectively reviewed from the hospital archive. The NGS panel included 11 mTOR-pathway-related genes with maximum coverage of 2000x. The detected variants were validated by digital droplet PCR.Pathogenic MTOR variants were identified in 10 patients (50%). Further comparison with MTOR-wildtype FCDIIb suggested a profound genotype-phenotype association characterized by (1) a non-temporal lobe lesion on MRI, (2) a larger lesion volume occupying grey and white matter (3.032±1.859cm3 vs. 1.110±0.856cm3 , p=0.014), (3) more balloon cells (50.20±14.40BC/mm2 vs. 31.64±30.56BC/mm2 , p=0.099) and dysmorphic neurons (48.72±19.47DN/mm2 vs. 15.28±13.95DN/mm2 , p=0.000), as well as (4) a positive correlation between VAF and the lesion volume (r=0.802, p=0.017).Our study identified frequent MTOR mutations in the cell-rich FCDIIb phenotype, clinically characterized by a non-temporal location and large lesion volume. Comprehensive genotype-phenotype associations will help us further explore and define the broad spectrum of FCD lesions to make more targeted therapies available in the realm of epileptology.This article is protected by copyright. All rights reserved.
基金：
National Natural Science Foundation of China (Grant No. 81771395 to TY), Beijing Natural Science Foundation (Grant No. L182015 to GZ), Beijing Hospitals Authority Ascent Plan (Grant No. DFL20190801 to GZ and YP), Capital Health Research and Development Special Project (Grant No. 2020-1-2013 to GZ), National Support for Provincial Major Disease Medical Services and Social Capability Enhancement Project (YW and YP).
第一作者机构：[1]Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.[2]Clinical Research Center for Epilepsy, Xuanwu Hospital, Beijing, 100053, China.[3]National Center for Neurological Disorders, Beijing, 100053, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.[2]Clinical Research Center for Epilepsy, Xuanwu Hospital, Beijing, 100053, China.[3]National Center for Neurological Disorders, Beijing, 100053, China.[4]Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.[5]Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.[*1]Department of Pathology[*2]Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China[*3]Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Wang Yajie,Yu Tao,mcke Ingmar,et al.The clinico-pathological characterization of Focal Cortical Dysplasia type IIb genetically defined by MTOR mosaicism[J].NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY.2023,49(1):doi:10.1111/nan.12874.
APA：
Wang Yajie,Yu Tao,mcke Ingmar,Cai Yanning,Sun Ke...&Piao Yueshan.(2023).The clinico-pathological characterization of Focal Cortical Dysplasia type IIb genetically defined by MTOR mosaicism.NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY,49,(1)
MLA：
Wang Yajie,et al."The clinico-pathological characterization of Focal Cortical Dysplasia type IIb genetically defined by MTOR mosaicism".NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY 49..1(2023)
