Liu Yo-Tsen, Lee Yi-Chung, Yang Chih-Chao, Chen Mai-Ling, Lin Kon-Ping
The Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
J Neurol Sci. 2008 Apr 15;267(1-2):91-9. doi: 10.1016/j.jns.2007.10.011. Epub 2007 Nov 26.
Transthyretin (TTR) variants of familial amyloid neuropathies (FAP) form a heterogenous group of autosomal dominantly inherited diseases. TTR gene analysis in several nationalities (Japanese, Portuguese, French, and British) has shown many distinguishing characteristics in the genotype-phenotype correlation. In Chinese, there are only a few reports of private TTR gene mutations belonging to single kindred.
We collected five patients with autosomal dominant inheritant sensorimotor polyneuropathy and tissue-proved amyloid deposition. The diagnosis of FAP was established on the mutation of the TTR gene detected by direct sequencing. Haplotype analysis was conducted in four of these patients.
These five FAP patients shared an identical missense mutation, Ala97Ser, in the TTR gene. This mutation presented with a constellation of late-onset polyneuropathy, preceding carpal tunnel syndrome, and outstanding autonomic dysfunction. Heart was the most frequently involved vital organ. Haplotype analysis hinted independent origins although the numbers were limited. Our study is the first case series gathering from the Chinese-Taiwanese population. We proposed a possible hot-spot mutation of the TTR gene, Ala97Ser, in this ethnic.
家族性淀粉样神经病（FAP）的转甲状腺素蛋白（TTR）变体构成一组常染色体显性遗传疾病的异质性群体。对多个民族（日本人、葡萄牙人、法国人及英国人）的TTR基因分析显示，在基因型-表型相关性方面存在许多显著特征。在中国，仅有少数关于单个家族中TTR基因突变的报道。
我们收集了5例常染色体显性遗传性感觉运动性多神经病患者，且组织学证实有淀粉样沉积。通过直接测序检测到TTR基因突变后确诊为FAP。对其中4例患者进行了单倍型分析。
这5例FAP患者在TTR基因中共享一个相同的错义突变，即Ala97Ser。该突变表现为迟发性多神经病、腕管综合征前驱症状以及显著自主神经功能障碍的一系列症状。心脏是最常受累的重要器官。尽管样本数量有限，但单倍型分析提示其起源独立。我们的研究是首个来自中国台湾人群的病例系列。我们提出在该民族中TTR基因可能存在一个热点突变，即Ala97Ser。
