| Literature DB >> 22693999 |
Sophie Valleix1, Julian D Gillmore, Frank Bridoux, Palma P Mangione, Ahmet Dogan, Brigitte Nedelec, Mathieu Boimard, Guy Touchard, Jean-Michel Goujon, Corinne Lacombe, Pierre Lozeron, David Adams, Catherine Lacroix, Thierry Maisonobe, Violaine Planté-Bordeneuve, Julie A Vrana, Jason D Theis, Sofia Giorgetti, Riccardo Porcari, Stefano Ricagno, Martino Bolognesi, Monica Stoppini, Marc Delpech, Mark B Pepys, Philip N Hawkins, Vittorio Bellotti.
Abstract
We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.Entities:
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Year: 2012 PMID： 22693999 DOI： 10.1056/NEJMoa1201356
Source DB: PubMed Journal: N Engl J Med ISSN： 0028-4793 Impact factor: 91.245