Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I
Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I
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DOI：
10.1046/j.1523-1755.1998.00770.x
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发表时间：
1998-02-01
影响因子：
19.6
通讯作者：
Pepys, MB
中科院分区：
文献类型：
--
作者：
Persey, MR;Booth, DR;Pepys, MB
我们报告一个三代常染色体显性遗传性全身性淀粉样变性家族，表现为肾脏受累。这一代的两位成员在16和18年前因终末期肾衰竭接受了肾脏移植，尽管存在大量内脏淀粉样变性，但临床表现仍然良好。这一代的另外两名成员，年龄分别为32岁和47岁，有大量的系统性淀粉样蛋白，但没有临床残疾。已知在前几代受影响的个体在成年早期死于肾衰竭。先证者（移植个体之一）的淀粉样蛋白沉积由载脂蛋白a - i （apoA-I）组成，在在世的家族成员中，淀粉样蛋白沉积与apoA-I基因4外显子出现一个新的9个碱基对框内缺失突变完全一致，导致残基Glu70Phe71Trp72缺失。这预示着成熟的apoA-I获得了一个额外的正电荷，这种变体在所有携带者的血浆中都被检测到。所有先前报道的apoA-I的淀粉样变异体也携带一个额外的正电荷，这表明这种静电变化可能与apoA-I的淀粉样变性有关。
We report a family with autosomal-dominant hereditary systemic amyloidosis in three generations, presenting with renal involvement. Two members of the current generation received renal transplants for end-stage renal failure 16 and 18 years ago, and remain ver, well clinically despite massive visceral amyloidosis. Two other members of this generation, aged 32 and 47 years, have massive systemic amyloid but no clinical disability. Individuals known to be affected in previous generations died of renal failure in early adult life. Amyloid deposits in the proband, one of the transplanted individuals, were composed of apolipoprotein A-I (apoA-I), and among living family members there was complete concordance between amyloidosis and the presence of a novel 9 base pair in-frame deletion mutation in exon 4 of the apoA-I gene, causing a loss of residues Glu70Phe71Trp72. This predicts the acquisition of a single extra positive charge by mature apoA-I, and this variant was detected in the plasma of all carriers. All the previously reported amyloidogenic variants of apoA-I also carry an extra positive charge, indicating that this electrostatic change is likely to be relevant to the amyloidogenicity of apoA-I.