Abstract

Till date, there had been no reported case of dialysis-related amyloidosis (DRA) associated with a β₂-microglobulin variant. We report here a 41-year-old haemodialysis patient with systemic amyloidosis, exhibiting macroglossia and swelling salivary glands, uncommon clinical manifestations for DRA. Molecular analysis showed that the patient had a new variant of β₂-microglobulin (V27M). Extracted amyloid protein was predominantly composed of variant β₂-microglobulin. In vitro analysis revealed that this variant β₂-microglobulin had a strong amyloidogenic propensity, probably owing to the decreased stability caused by a bulky methionine residue. Our data clearly show that V27M variant is amyloidogenic and this mutation results in unusual clinical manifestations. To date, only one amyloidogenic β₂-microglobulin variant (D76N) has been reported in non-dialysis patients. It is noteworthy that the V27M and D76N variants show substantial differences in both clinical phenotypes and pathomechanical features. This is the first case of DRA associated with a naturally occurring β₂-microglobulin variant.

摘要

迄今为止，尚无与 β _{2 -}微球蛋白变体相关的透析相关淀粉样变性 (DRA) 病例的报告。我们在此报告一名 41 岁的血液透析患者，患有系统性淀粉样变性，表现出巨舌症和肿胀的唾液腺，这是 DRA 的罕见临床表现。分子生物学研究表明，患者有β的新变种₂微球蛋白（V27M）。提取的淀粉样蛋白主要由变体的β ₂ -微球蛋白。体外分析表明，这种变异 β ₂β-微球蛋白具有很强的淀粉样蛋白生成倾向，这可能是由于大量蛋氨酸残基导致稳定性降低。我们的数据清楚地表明 V27M 变异是淀粉样蛋白原性的，这种突变会导致不寻常的临床表现。迄今为止，在非透析患者中​​仅报道了一种淀粉样蛋白 β _{2 -}微球蛋白变异 (D76N)。值得注意的是，V27M 和 D76N 变体在临床表型和病理力学特征上均显示出显着差异。这是第一例与天然存在的 β _{2 -}微球蛋白变体相关的 DRA 病例。