Hereditary systemic immunoglobulin light-chain amyloidosis

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

Immunoglobulin Light Chains
Amyloidosis
Amyloid
Mutation
Genes
Light
Amyloidogenic Proteins
Amino Acids
Chemotherapy
Dialysis
Familial Amyloidosis
Cytosine
DNA
Guanine
Serine
Paraproteinemias
Cysteine
Blood Proteins
Protein Sequence Analysis
Diagnostic Errors

ASJC Scopus subject areas

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

Cite this

Hereditary systemic immunoglobulin light-chain amyloidosis. / Benson, Merrill; Liepnieks, Juris J.; Kluve-Beckerman, Barbara.

In: Blood, Vol. 125, No. 21, 2015, p. 3281-3286.

Research output: Contribution to journalArticle

Benson, M, Liepnieks, JJ & Kluve-Beckerman, B 2015, 'Hereditary systemic immunoglobulin light-chain amyloidosis', Blood, vol. 125, no. 21, pp. 3281-3286. https://doi.org/10.1182/blood-2014-12-618108
Benson, Merrill ; Liepnieks, Juris J. ; Kluve-Beckerman, Barbara. / Hereditary systemic immunoglobulin light-chain amyloidosis. In: Blood. 2015 ; Vol. 125, No. 21. pp. 3281-3286.
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