A new human hereditary amyloidosis: The result of a stop-codon mutation in the apolipoprotein AII gene

Merrill Benson, Juris J. Liepnieks, Masahide Yazaki, Taro Yamashita, Kamran Hamidi Asl, Brian Guenther, Barbara Kluve-Beckerman

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Hereditary systemic amyloidosis may be caused by mutations in a number of plasma proteins including transthyretin, apolipoprotein AI, fibrinogen Aα-chain, lysozyme, and gelsolin. Each type of amyloidosis is inherited as an autosomal dominant disease and is associated with a structurally altered protein that aggregates to form amyloid fibrils. Here we report that the amyloid protein in a family with previously uncharacterized hereditary renal amyloidosis is apolipoprotein AII (apoAII) with a 21-residue peptide extension on the carboxyl terminus. Sequence analysis of the apoAII gene of affected individuals showed heterozygosity for a single base substitution in the apoAII stop codon. The mutation results in extension of translation to the next in-frame stop codon 60 nucleotides downstream and is predicted to give a 21-residue C-terminal extension of the apoAII protein identical to that found in the amyloid. This mutation produces a novel BstNI restriction site that can be used to identify individuals with this gene by restriction fragment length polymorphism analysis. This is the first report of apoAII amyloid in humans and the first mutation identified in apoAII protein. Amyloid fibril formation from apoAII suggests that this lipoprotein, which is predicted to have an amphipathic helical structure, must undergo a transition to a β-pleated sheet by a mechanism shared by other lipoproteins that form amyloid.

Original languageEnglish
Pages (from-to)272-277
Number of pages6
JournalGenomics
Volume72
Issue number3
DOIs
StatePublished - Mar 15 2001

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Familial Amyloidosis
Apolipoprotein A-II
Terminator Codon
Apolipoproteins
Amyloid
Mutation
Genes
Lipoproteins
Gelsolin
Amyloidogenic Proteins
Prealbumin
Apolipoprotein A-I
Amyloidosis
Muramidase
Restriction Fragment Length Polymorphisms
Fibrinogen
Sequence Analysis
Blood Proteins
Proteins
Nucleotides

ASJC Scopus subject areas

  • Genetics

Cite this

Benson, M., Liepnieks, J. J., Yazaki, M., Yamashita, T., Hamidi Asl, K., Guenther, B., & Kluve-Beckerman, B. (2001). A new human hereditary amyloidosis: The result of a stop-codon mutation in the apolipoprotein AII gene. Genomics, 72(3), 272-277. https://doi.org/10.1006/geno.2000.6499

A new human hereditary amyloidosis : The result of a stop-codon mutation in the apolipoprotein AII gene. / Benson, Merrill; Liepnieks, Juris J.; Yazaki, Masahide; Yamashita, Taro; Hamidi Asl, Kamran; Guenther, Brian; Kluve-Beckerman, Barbara.

In: Genomics, Vol. 72, No. 3, 15.03.2001, p. 272-277.

Research output: Contribution to journalArticle

Benson, M, Liepnieks, JJ, Yazaki, M, Yamashita, T, Hamidi Asl, K, Guenther, B & Kluve-Beckerman, B 2001, 'A new human hereditary amyloidosis: The result of a stop-codon mutation in the apolipoprotein AII gene', Genomics, vol. 72, no. 3, pp. 272-277. https://doi.org/10.1006/geno.2000.6499
Benson, Merrill ; Liepnieks, Juris J. ; Yazaki, Masahide ; Yamashita, Taro ; Hamidi Asl, Kamran ; Guenther, Brian ; Kluve-Beckerman, Barbara. / A new human hereditary amyloidosis : The result of a stop-codon mutation in the apolipoprotein AII gene. In: Genomics. 2001 ; Vol. 72, No. 3. pp. 272-277.
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