Chen W, Xie Y, Zheng M, Lin J, Huang P, Pei Z, Yao X
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No.58 Zhongshan Road 2, Guangzhou 510080, China.
Eur J Neurol. 2020 Jun;27(6):1017-1022. doi: 10.1111/ene.14213. Epub 2020 Apr 10.
Amyotrophic lateral sclerosis (ALS)-related genes and mutations have been increasingly discovered recently and an improved understanding of genotype-phenotype relationships may help to predict the disease course and refine genetic diagnosis.
We collected clinical data and blood samples from 268 patients and used next-generation sequencing to comprehensively assay genetic variations in a panel of known ALS genes from 2015 to 2019.
Among these patients, the mean age of onset was 52.30 ± 10.42 years with a mean diagnosis delay of 15.90 ± 11.88 months. Patients with SOD1, TARDBP and FUS variants were more likely to suffer from familial ALS. Additionally, carriers of FUS variants displayed the earliest onset, followed by those with SOD1 variants. Patients with NEFH variants showed a closer link to pesticide exposure. Patients with SETX variants were prone to bulbar onset with moderate anxiety problems. No genotype-phenotype relations were found in SPG11 and ERBB4 mutants.
Our findings uncovered some genotype-phenotype relationships and may help to predict the disease course of patients with ALS in southern China.
肌萎缩侧索硬化症（ALS）相关基因及突变近来不断被发现，对基因型 - 表型关系的深入理解可能有助于预测疾病进程并优化基因诊断。
我们收集了268例患者的临床资料和血液样本，并于2015年至2019年使用二代测序技术全面检测一组已知ALS基因中的基因变异。
在这些患者中，平均发病年龄为52.30±10.42岁，平均诊断延迟为15.90±11.88个月。携带超氧化物歧化酶1（SOD1）、反式激活反应DNA结合蛋白（TARDBP）和融合蛋白（FUS）变异的患者更易患家族性ALS。此外，FUS变异携带者发病最早，其次是SOD1变异携带者。携带神经丝重链（NEFH）变异的患者与接触农药的关联更为密切。携带SETX变异的患者易出现延髓起病并伴有中度焦虑问题。在痉挛性截瘫11型（SPG11）和表皮生长因子受体4（ERBB4）突变体中未发现基因型 - 表型关系。
我们的研究结果揭示了一些基因型 - 表型关系，可能有助于预测中国南方ALS患者的疾病进程。
