title: Hereditary systemic immunoglobulin light-chain amyloidosis.
abstract: Several members of a family died from renal failure as a result of systemic amyloidosis. Extensive studies to detect previously documented gene mutations associated with amyloidosis failed to identify a causative factor. In search of the genetic basis for this syndrome, amyloid fibrils were isolated from renal tissue of a member of the kin who died while on renal dialysis. Amino acid sequencing of isolated amyloid protein identified sequences compatible with the constant region of the immunoglobulin κ light-chain. Isolation and characterization of κ light-chain protein from serum of an affected member of the kindred revealed mutation in the constant region of κ light-chain, with cysteine replacing serine at amino acid residue 131. This mutation (Ser131Cys) was confirmed by DNA analysis, which identified a single-base change of cytosine to guanine at the second position of codon 131 of the κ light-chain gene (TCT131TGT). DNA analysis of members of the extended family revealed transmission of the Ser131Cys mutation and association with systemic amyloidosis. This amyloid light-chain (AL) amyloidosis, which is a hereditary type of amyloidosis and not the result of a monoclonal plasma cell dyscrasia, may be misdiagnosed and lead to inappropriate chemotherapy.
authors: Indiana University School of Medicine, Department of Pathology and Laboratory Medicine, Indianapolis, IN: and Richard L. Roudebush VA Medical Center, Indianapolis, IN.
authors: Merrill D
authors: MD
authors: Benson
authors: Indiana University School of Medicine, Department of Pathology and Laboratory Medicine, Indianapolis, IN: and.
authors: Juris J
authors: JJ
authors: Liepnieks
authors: Indiana University School of Medicine, Department of Pathology and Laboratory Medicine, Indianapolis, IN: and.
authors: Barbara
authors: B
authors: Kluve-Beckerman
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D007145:Immunoglobulin kappa-Chains