a Department of Neurology, Graduate School of Medical Sciences , Kumamoto University , Kumamoto , Japan.
Amyloid. 2018 Sep;25(3):143-147. doi: 10.1080/13506129.2018.1531842.
Hereditary transthyretin (ATTRm) amyloidosis, formerly known as familial amyloid polyneuropathy, is a major type of hereditary systemic amyloidosis, in which the disease is caused by mutant transthyretin (TTR). Although more than 140 different point mutations have been identified in the TTR gene, ATTRm amyloidosis patients with the TTR Val30Met mutation are most frequently found worldwide. Interestingly, the onset age of the ATTR Val30Met amyloidosis is highly varied among countries and regions. The reason for these differences in onset age and penetrance remains to be elucidated. We recently performed an epidemiological study to analyze the clinical and genetic characteristics of ATTRm amyloidosis patients in Japan. Our results led us to the following questions: Why did most of the non-endemic patients with the same TTR Val30Met mutation not have a family history of the disease, a typical autosomal dominant hereditary disorder? Why does ATTR Val30Met amyloidosis alone demonstrate foci of occurrence? Why is only this type of ATTRm amyloidosis nationally and globally distributed? In this mini-review, we discuss these unanswered questions based on recent genetic epidemiological studies on ATTR Val30Met amyloidosis.
遗传性转甲状腺素蛋白（ATTR）淀粉样变性，以前称为家族性淀粉样多神经病，是一种主要的遗传性系统性淀粉样变性，其病因是转甲状腺素蛋白（TTR）突变。尽管在 TTR 基因中已经发现了超过 140 种不同的点突变，但在全世界范围内，ATTRm 淀粉样变性患者中最常见的是 TTR Val30Met 突变。有趣的是，ATTR Val30Met 淀粉样变性的发病年龄在不同国家和地区存在很大差异。这些发病年龄和外显率差异的原因仍有待阐明。我们最近进行了一项流行病学研究，分析了日本 ATTRm 淀粉样变性患者的临床和遗传特征。我们的研究结果提出了以下问题：为什么大多数患有相同 TTR Val30Met 突变的非流行地区患者没有该病的家族史，而该病是一种典型的常染色体显性遗传性疾病？为什么ATTR Val30Met 淀粉样变性仅表现为发病灶？为什么只有这种类型的 ATTRm 淀粉样变性在全国和全球范围内分布？在这篇小型综述中，我们根据最近关于 ATTR Val30Met 淀粉样变性的遗传流行病学研究，讨论了这些未解决的问题。
