Dialysis-related amyloidosis associated with a novel β2-microglobulin variant

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.