A novel substitution of proline (P32L) destabilises β2-microglobulin inducing hereditary systemic amyloidosis.
Amyloid-forming propensity
P32L variant
β2M amyloidosis
β2M gene mutation
Journal
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
ISSN: 1744-2818
Titre abrégé: Amyloid
Pays: England
ID NLM: 9433802
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
pubmed:
17
5
2022
medline:
3
1
2023
entrez:
16
5
2022
Statut:
ppublish
Résumé
β2-microglobulin amyloidosis was first described in the 1980s as a protein deposition disease associated with long-term haemodialysis. More recently, two inherited forms resulting from separate point mutations in the β2-microglobulin gene have been identified. In this report, we detail a novel β2M variant, P32L, caused by a unique dinucleotide mutation that is linked to systemic hereditary β2-microglobulin amyloidosis. Three family members from a Portuguese kinship featured cardiomyopathy, requiring organ transplantation in one case, along with soft tissue involvement; other involvements included gastrointestinal, neuropathic and sicca syndrome. The P32L variant was caused by the unique heterozygous dinucleotide mutation c.154_155delinsTT. Amyloid disease featured lowered serum β2-microglobulin levels with near equal amounts of circulating P32L and wild-type proteins; amyloid deposits were composed exclusively of P32L variant protein. This work provides both clinical and experimental evidence supporting the critical role of P32 residue replacement in β2M amyloid fibrillogenesis.
Sections du résumé
BACKGROUND
UNASSIGNED
β2-microglobulin amyloidosis was first described in the 1980s as a protein deposition disease associated with long-term haemodialysis. More recently, two inherited forms resulting from separate point mutations in the β2-microglobulin gene have been identified. In this report, we detail a novel β2M variant, P32L, caused by a unique dinucleotide mutation that is linked to systemic hereditary β2-microglobulin amyloidosis.
METHODS
UNASSIGNED
Three family members from a Portuguese kinship featured cardiomyopathy, requiring organ transplantation in one case, along with soft tissue involvement; other involvements included gastrointestinal, neuropathic and sicca syndrome.
RESULTS
UNASSIGNED
The P32L variant was caused by the unique heterozygous dinucleotide mutation c.154_155delinsTT. Amyloid disease featured lowered serum β2-microglobulin levels with near equal amounts of circulating P32L and wild-type proteins; amyloid deposits were composed exclusively of P32L variant protein.
CONCLUSIONS
UNASSIGNED
This work provides both clinical and experimental evidence supporting the critical role of P32 residue replacement in β2M amyloid fibrillogenesis.
Identifiants
pubmed: 35575118
doi: 10.1080/13506129.2022.2072199
doi:
Substances chimiques
Amyloid
0
beta 2-Microglobulin
0
Proline
9DLQ4CIU6V
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM