癫痫手术患者切除脑组织的体细胞变异分析。

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2024-10-26 DOI:10.1111/epi.18148
Maurits W C B Sanders, Bobby P C Koeleman, Eva H Brilstra, Floor E Jansen, Sara Baldassari, Mathilde Chipaux, Nam Suk Sim, Ara Ko, Hoon-Chul Kang, Ingmar Blümcke, Dennis Lal, Stéphanie Baulac, Jeong Ho Lee, Eleonora Aronica, Kees P J Braun
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引用次数: 0

摘要

我们研究了2015年至2020年期间在乌得勒支大学医学中心(荷兰)接受手术的皮质发育畸形(MCD)癫痫手术患者(疑似)的种系变异和体细胞变异的分布情况,并将我们的数据与之前发表的四项队列研究进行了汇总。在 663 例合并病例中,有 203 例(31%)通过组织分析发现了致病变体。在379例局灶性皮质发育不良(FCD)II型病例中的126例(33%)和37例半身不遂病例中的23例(62%)中,发现了致病变体,其中大部分涉及mTOR信号通路。在178例(27%)伴少突胶质增生和癫痫的FCDI/轻度MCD/MMCD病例中,有48例发现了10个局灶性癫痫基因的致病变体;其中36例(75%)是SLC35A2变体。69例(9%)无组织病理学病变的患者中,有6例(9%)存在SLC35A2(5例)或DEPDC5(1例)致病变异。所有在组织中存在致病变异的病例中,血液DNA中的种系变异均得到证实,变异等位基因频率(VAF)约为50%。在组织中存在体细胞变异的 114 例患者中,有 7 例(6%)在血液中检测到嵌合体。半数以上的致病性体细胞变异的等位基因频率(VAF
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Somatic variant analysis of resected brain tissue in epilepsy surgery patients.

We studied the distribution of germline and somatic variants in epilepsy surgery patients with (suspected) malformations of cortical development (MCD) who underwent surgery between 2015 and 2020 at University Medical Center Utrecht (the Netherlands) and pooled our data with four previously published cohort studies. Tissue analysis yielded a pathogenic variant in 203 of 663 (31%) combined cases. In 126 of 379 (33%) focal cortical dysplasia (FCD) type II cases and 23 of 37 (62%) hemimegalencephaly cases, a pathogenic variant was identified, mostly involving the mTOR signaling pathway. Pathogenic variants in 10 focal epilepsy genes were found in 48 of 178 (27%) FCDI/mild MCD/mMCD with oligodendroglial hyperplasia and epilepsy cases; 36 of these (75%) were SLC35A2 variants. Six of 69 (9%) patients without a histopathological lesion had a pathogenic variant in SLC35A2 (n = 5) or DEPDC5 (n = 1). A germline variant in blood DNA was confirmed in all cases with a pathogenic variant in tissue, with a variant allele frequency (VAF) of ~50%. In seven of 114 patients (6%) with a somatic variant in tissue, mosaicism in blood was detected. More than half of pathogenic somatic variants had a VAF < 5%. Further analysis of the correlation between genetic variants and surgical outcomes will improve patient counseling and may guide postoperative treatment decisions.

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来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
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