SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.
SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.
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DOI：
10.1093/brain/awp325
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Kawarai T
中科院分区：
文献类型：
--
作者：
Orlacchio A;Babalini C;Borreca A;Patrono C;Massa R;Basaran S;Munhoz RP;Rogaeva EA;St George-Hyslop PH;Bernardi G;Kawarai T
spatacsin基因突变是常染色体隐性遗传痉挛性截瘫伴胼胝体薄的最常见原因。肌萎缩性侧索硬化症和遗传性痉挛性截瘫之间的共同临床、病理和遗传特征促使我们研究了25个常染色体隐性幼年肌萎缩性侧索硬化症家族和spatascin基因突变的长期生存率。纳入标准是根据修订的El Escorial标准诊断为临床明确的肌萎缩性侧索硬化症。排除标准是诊断为遗传性痉挛性截瘫，胼胝体薄，符合既定方案。还进行了额外的病理和遗传评估。令人惊讶的是，在10个不相关的常染色体隐性幼年肌萎缩性侧索硬化症家系中发现了12个spatacsin基因序列改变（其中一个是新的，IVS30 + 1 G > A）。这些家庭的原籍国是意大利、巴西、加拿大、日本和土耳其。这些变异似乎是致病的，因为它们在所有谱系中都与疾病共分离，在对照组中不存在，并且在这些家族中有中枢神经系统组织的一个成员中与肌萎缩侧索硬化症神经病理学有关。我们的研究表明，spatascin基因突变可能导致比以前认识到的更广泛的临床特征，包括常染色体隐性青少年肌萎缩性侧索硬化症。
The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.
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