Department of Neurology, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Department of Neurology, Eskişehir City Hospital, Eskişehir, Turkey.
Acta Neurol Belg. 2020 Dec;120(6):1411-1418. doi: 10.1007/s13760-020-01441-z. Epub 2020 Jul 15.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease leading to motor neuron damage. In this study, the clinical, demographic, and genetic features of ALS patients in the city of Sakarya, Turkey, were investigated. Patients with an established diagnosis of ALS according to the Awaji criteria were included. Age, sex, age at onset of ALS, initial complaints, consanguineous marriage, and genetic features were retrospectively investigated. Conventional genetic analysis and NGS were used for molecular evaluation of patients. A total of 55 probands (10 familial, 45 sporadic) in whom ALS was suspected due to their phenotypic features were included. Thirty-two patients were male (58.2%), and 23 were female (41.8%); their mean ages were 62.65 ± 13 years. The mean age of onset for 37 familial patients from 10 families was 49.9 years. Two cases had juvenile-onset. Fourteen (25.5%) bulbar-onset versus 40 (72.7%) limb-onset patients were detected; one patient had both. Six (10.9%) patients showed marked frontotemporal dementia. Twenty-nine (52.7%) patients died during the follow-up period. Genetic analysis identified causative variants in eleven cases, carrying variants in six different ALS genes (C9orf72, SOD1, VCP, SPG11, TBK1, and SH3TC2). Genetic investigations have revealed more than 40 genes to be involved in the pathogenesis of ALS. Our relatively small study cohort restricted to one province of Turkey, however, prone to migration, consists of 10/55 familial ALS cases, which harbor two rare (SH3TC2-p.Met523Thr and TBK1-p.Glu643del) and two novel (SPG11-p.Lys656Valfs*11 and VCP-p.Arg191Pro) mutations contributing to the literature.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，导致运动神经元损伤。在这项研究中，研究了土耳其萨卡里亚市 ALS 患者的临床、人口统计学和遗传特征。根据 Awaji 标准，纳入了确诊为 ALS 的患者。回顾性调查了患者的年龄、性别、ALS 发病年龄、首发症状、近亲结婚和遗传特征。对患者进行了常规基因分析和 NGS 分子评估。共纳入 55 名疑诊 ALS 的先证者（10 例家族性，45 例散发性），这些患者的表型特征提示 ALS。32 例为男性（58.2%），23 例为女性（41.8%），平均年龄为 62.65±13 岁。10 个家系的 37 例家族性患者的平均发病年龄为 49.9 岁。有 2 例为少年型。40 例（72.7%）为肢体起病，14 例（25.5%）为延髓起病，1 例为二者兼有。6 例（10.9%）患者表现为明显的额颞叶痴呆。29 例（52.7%）患者在随访期间死亡。基因分析在 11 例患者中发现了致病变异，这些变异存在于 6 个不同的 ALS 基因（C9orf72、SOD1、VCP、SPG11、TBK1 和 SH3TC2）中。遗传研究已经发现了 40 多个基因参与 ALS 的发病机制。然而，我们的研究队列相对较小，仅限于土耳其的一个省，而且容易发生移民，包括 10/55 例家族性 ALS 病例，其中有两个罕见的（SH3TC2-p.Met523Thr 和 TBK1-p.Glu643del）和两个新的（SPG11-p.Lys656Valfs*11 和 VCP-p.Arg191Pro）突变，这在文献中有所报道。
