A new human hereditary amyloidosis: The result of a stop-codon mutation in the apolipoprotein AII gene
A new human hereditary amyloidosis: The result of a stop-codon mutation in the apolipoprotein AII gene
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DOI：
10.1006/geno.2000.6499
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发表时间：
2001-03-15
期刊：
影响因子：
4.4
通讯作者：
Kluve-Beckerman, B
中科院分区：
文献类型：
--
作者：
Benson, MD;Liepnieks, JJ;Kluve-Beckerman, B
遗传性系统性淀粉样变性可由多种血浆蛋白突变引起，包括甲状腺素运载蛋白、载脂蛋白AI、纤维蛋白原A α链、溶菌酶和凝溶胶蛋白。每种类型的淀粉样变性都是作为常染色体显性遗传疾病遗传的，并且与聚集形成淀粉样纤维的结构改变的蛋白质有关。在这里，我们报告的淀粉样蛋白在一个家庭与以前的特点遗传性肾淀粉样变性是载脂蛋白AII（apoAII）与21个残基的肽延伸的羧基末端。受影响的个人的apoAII基因的序列分析表明，在apoAII终止密码子的一个单一的碱基取代杂合性。该突变导致翻译延伸到下游60个核苷酸的下一个符合读框的终止密码子，并预测得到与淀粉样蛋白中发现的相同的apoAII蛋白的gl-残基C-末端延伸。这种突变产生了一个新的BstNI限制性位点，可用于通过限制性片段长度多态性分析鉴定具有该基因的个体。这是人类apoAII淀粉样蛋白的首次报道，也是apoAII蛋白的首次突变。由apoAII形成淀粉样原纤维表明，这种被预测具有两亲性螺旋结构的脂蛋白必须通过形成淀粉样蛋白的其它脂蛋白所共有的机制转变为β-折叠片层. (C)北京：科学出版社.
Hereditary systemic amyloidosis may be caused by mutations in a number of plasma proteins including transthyretin, apolipoprotein AI, fibrinogen A alpha -chain, lysozyme, and gelsolin. Each type of amyloidosis is inherited as an autosomal dominant disease and is associated with a structurally altered protein that aggregates to form amyloid fibrils. Here we report that the amyloid protein in a family with previously uncharacterized hereditary renal amyloidosis is apolipoprotein AII (apoAII) with a 21-residue peptide extension on the carboxyl terminus. Sequence analysis of the apoAII gene of affected individuals showed heterozygosity for a single base substitution in the apoAII stop codon. The mutation results in extension of translation to the next in-frame stop codon 60 nucleotides downstream and is predicted to give a gl-residue C-terminal extension of the apoAII protein identical to that found in the amyloid. This mutation produces a novel BstNI restriction site that can be used to identify individuals with this gene by restriction fragment length polymorphism analysis. This is the first report of apoAII amyloid in humans and the first mutation identified in apoAII protein. Amyloid fibril formation from apoAII suggests that this lipoprotein, which is predicted to have an amphipathic helical structure, must undergo a transition to a beta -pleated sheet by a mechanism shared by other lipoproteins that form amyloid. (C) 2001 Academic Press.