Hereditary systemic immunoglobulin light-chain amyloidosis

Merrill Benson, Juris J. Liepnieks, Barbara Kluve-Beckerman

Research output: Contribution to journalArticle

6 Scopus citations

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 kκlight-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.

Original languageEnglish (US)
Pages (from-to)3281-3286
Number of pages6
JournalBlood
Volume125
Issue number21
DOIs
StatePublished - 2015

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Medicine(all)
  • Hematology
  • Cell Biology

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