Dialysis-related amyloidosis associated with a novel β2-microglobulin variant. (2nd January 2021)

• Record Type: Journal Article
• Authors: Mizuno, Hiroki; Hoshino, Junichi; So, Masatomo; Kogure, Yuta; Fujii, Takeshi; Ubara, Yoshifumi; Takaichi, Kenmei; Nakaniwa, Tetsuko; Tanaka, Hideaki; Kurisu, Genji; Kametani, Fuyuki; Nakagawa, Mayuko; Yoshinaga, Tsuneaki; Sekijima, Yoshiki; Higuchi, Keiichi; Goto, Yuji; Yazaki, Masahide
• Is Part Of: Amyloid. Volume 28:Number 1(2021)
• Page Start: 42
• Page End: 49
• Publication Date: 2021-01-02
• Subjects: Dialysis-related amyloidosis -- disulphide bond -- variant β2-microglobulin -- wild-type β2-microglobulin; Amyloidosis -- Periodicals; 616.3995
• DOI: 10.1080/13506129.2020.1813097
• Languages: English
• ISSNs: 1350-6129

Abstract

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.