Genetic analysis of patients with familial and sporadic amyotrophic lateral sclerosis in a Brazilian Research Center

IF 2.5 4区医学 Q2 CLINICAL NEUROLOGY

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Pub Date : 2017-04-03 DOI:10.1080/21678421.2016.1254245

G. Chadi, J. R. Maximino, F. Jorge, Fabrício Castro de Borba, J. M. Gilio, D. Callegaro, C. G. Lopes, Samantha Nakamura Dos Santos, G. Rebelo

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引用次数: 30

Abstract

Abstract Objective: To investigate gene mutations in familial form (FALS) and sporadic form (SALS) of amyotrophic lateral sclerosis (ALS) in a highly miscegenated population. Methods: Frequencies of mutations in the C9orfF72, TARDBP, SOD1, FUS and VAPB genes were investigated in a cohort of FALS (n = 39) and SALS (n = 189) subjects from the Research Centre of the University of São Paulo School of Medicine. All patients were subjected to C9orf72 and TARDBP analyses. SOD1, FUS and VAPB were also evaluated in FALS subjects. Results: Mutations were identified in FALS (61.3%) and SALS (5.3%) patients. Mutations in C9orf72 (12.8%, >45 GGGGCC hexanucleotide repeats), VAPB (43.6%, P56S) and SOD1 (7.7%, L145S) were identified in FALS subjects. Pathogenic C9orf72 expansions (2.64%) were identified in some SALS patients. Similar changes of TARDBP were found in SALS (2.64%) but not in FALS subjects. No FUS mutations were seen in any FALS subjects. Conclusions: TARDBP and C9orf72 mutations in this cohort were similar to those found in other centres worldwide. VAPB mutation (P56S) was highly prevalent in Brazilian FALS patients.

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巴西研究中心家族性和散发性肌萎缩侧索硬化症患者的基因分析

摘要目的:探讨家族型(FALS)和散发性(SALS)肌萎缩性侧索硬化症(ALS)在高混种人群中的基因突变。方法:对来自圣保罗大学医学院研究中心的FALS (n = 39)和SALS (n = 189)患者的C9orfF72、TARDBP、SOD1、FUS和VAPB基因突变频率进行研究。所有患者均接受C9orf72和TARDBP分析。测定FALS患者的SOD1、FUS和VAPB。结果:FALS(61.3%)和SALS(5.3%)患者中存在突变。在FALS患者中发现了C9orf72 (12.8%， bbbb45 GGGGCC六核苷酸重复序列)、VAPB (43.6%， P56S)和SOD1 (7.7%， L145S)突变。部分SALS患者存在致病性C9orf72扩增(2.64%)。SALS患者TARDBP也有类似的变化(2.64%)，而FALS患者则没有。在所有FALS受试者中未见FUS突变。结论:该队列中的TARDBP和C9orf72突变与全球其他中心的突变相似。VAPB突变(P56S)在巴西FALS患者中高度流行。

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来源期刊

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

10.70%

发文量

期刊介绍： Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration is an exciting new initiative. It represents a timely expansion of the journal Amyotrophic Lateral Sclerosis in response to the clinical, imaging pathological and genetic overlap between ALS and frontotemporal dementia. The expanded journal provides outstanding coverage of research in a wide range of issues related to motor neuron diseases, especially ALS (Lou Gehrig’s disease) and cognitive decline associated with frontotemporal degeneration. The journal also covers related disorders of the neuroaxis when relevant to these core conditions.