Nagano Isao, Murakami Tetsuro, Shiote Mito, Manabe Yasuhiro, Hadano Shinji, Yanagisawa Yoshiko, Ikeda Joh-E, Abe Koji
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Neurol Res. 2003 Jul;25(5):505-9. doi: 10.1179/016164103101201733.
ALS2 is an autosomal recessive form of amyotrophic lateral sclerosis (AR-ALS) with juvenile onset, and has been mostly found in North African and Middle Eastern countries. Deletion mutations in the coding exons of a new gene ALS2, encoding a protein with guanine-nucleotide exchange factor (GEF) domains, have recently been identified in ALS2 patients. These mutations are predicted to cause a loss of protein function, indicating that ALS2 is the causative gene underlying ALS2. To examine whether ALS2 is mutated in Japanese ALS patients sharing some characteristics of ALS2, we analyzed ALS2 gene from three patients with AR-ALS. While no deletion mutation was detected in the coding regions of ALS2 gene, several single-nucleotide polymorphisms (SNPs) that have been found in healthy controls as well as in Tunisian ALS2 patients were found mostly in intronic regions of the gene. These results suggest that deletion mutations in ALS2 gene detected in ALS2 patients seem to be uncommon in Japanese AR-ALS, and that SNPs in uncoding regions might possibly be relevant to predisposition to ALS.
ALS2是一种常染色体隐性遗传的少年型肌萎缩侧索硬化症（AR-ALS），主要在北非和中东国家被发现。最近在ALS2患者中鉴定出一个新基因ALS2编码外显子中的缺失突变，该基因编码一种具有鸟嘌呤核苷酸交换因子（GEF）结构域的蛋白质。这些突变预计会导致蛋白质功能丧失，表明ALS2是ALS2的致病基因。为了研究在具有ALS2某些特征的日本ALS患者中ALS2是否发生突变，我们分析了3例AR-ALS患者的ALS2基因。虽然在ALS2基因的编码区域未检测到缺失突变，但在健康对照以及突尼斯ALS2患者中发现的几个单核苷酸多态性（SNP）大多位于该基因的内含子区域。这些结果表明，在ALS2患者中检测到的ALS2基因缺失突变在日本AR-ALS中似乎并不常见，并且非编码区域的SNP可能与ALS易感性有关。
