FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion
FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion
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DOI：
10.1038/jhg.2010.16
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发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Itoyama, Yasuto
中科院分区：
文献类型：
--
作者：
Suzuki, Naoki;Aoki, Masashi;Itoyama, Yasuto
最近发现肉瘤融合基因（FUS，也称为脂肪肉瘤翻译基因）的突变与非洲、欧洲和美洲人群中的家族性肌萎缩侧索硬化症（FALS）相关。在一个日本家族中，我们发现了R521 C FUS突变，据报道，这是在各种种族背景中发现的。家系46名成员中有23例患者有家族史，阳性率100%。他们在平均35.3岁时出现肌无力，随后出现构音障碍、吞咽困难、痉挛和肌肉萎缩。平均死亡年龄为37.2岁。神经病理检查的索引情况下，发现显着萎缩的脑干被盖的特点是细胞质嗜碱性包涵体的脑干神经元。我们在日本筛选了40个FALS家系，发现FUS第14和15外显子有4个突变（S513 P，K510 E，R514 S，H517 P）。即使在亚洲人种中，伴有FUS突变的FALS也可能具有发病早、进展快和复发率高的共同特征，尽管在伴有S513 P突变的患者中是晚发性的。尸检发现多系统变性和胞浆嗜碱性包涵体。Journal of Human Genetics（2010）55，252-254; doi：10.1038/jhg.2010.16; 2010年3月12日在线发表
Mutations in the fused in sarcoma (FUS, also known as translated in liposarcoma) gene have been recently discovered to be associated with familial amyotrophic lateral sclerosis (FALS) in African, European and American populations. In a Japanese family with FALS, we found the R521C FUS mutation, which has been reported to be found in various ethnic backgrounds. The family history revealed 23 patients with FALS among 46 family members, suggesting a 100% penetrance rate. They developed muscle weakness at an average age of 35.3 years, followed by dysarthria, dysphagia, spasticity and muscle atrophy. The average age of death was 37.2 years. Neuropathological examination of the index case revealed remarkable atrophy of the brainstem tegmentum characterized by cytoplasmic basophilic inclusion bodies in the neurons of the brainstem. We screened 40 FALS families in Japan and found 4 mutations (S513P, K510E, R514S, H517P) in exon 14 and 15 of FUS. Even in Asian races, FALS with FUS mutations may have the common characteristics of early onset, rapid progress and high penetrance rate, although in patients with the S513P mutation it was late-onset. Degeneration in multiple systems and cytoplasmic basophilic inclusion bodies were found in the autopsied cases. Journal of Human Genetics (2010) 55, 252-254; doi:10.1038/jhg.2010.16; published online 12 March 2010