A frame shift mutation in the fibrinogen Aα chain gene in a kindred with renal amyloidosis

Tomoyuki Uemichi, Juris J. Liepnieks, Toshiyuki Yamada, Morie Gertz, Nils Bang, Merrill D. Benson

Research output: Contribution to journalArticle

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Abstract

A new American kindred with amyloidosis was found by single-strand conformation polymorphism analysis to have a mutation in the fibrinogen Aα chain gene. Affected members in this kindred have autosomal dominant amyloid nephropathy. DNA sequencing showed a single nucleotide deletion at the third base of codon 524 of the fibrinogen Aα chain gene (4904delG) that resulted in a frame shift and premature termination of the protein at codon 548. Antiserum was produced to a portion of the abnormal peptide predicted by the DNA sequence and amyloid deposits were immunohistologically proven to contain this abnormal peptide. Two of the propositus' 4 children were positive for the mutant fibrinogen Aα chain gene by restriction fragment length polymorphism analysis based on polymerase chain reaction. These two mutant gene carriers now in the second decade of life show no clinical symptoms of amyloidosis as yet but have lower plasma fibrinogen concentrations when compared with their normal siblings. This is the first description of a kindred with renal amyloidosis and low plasma fibrinogen and also the first report of amyloidosis caused by a frame shift mutation.

Original languageEnglish (US)
Pages (from-to)4197-4203
Number of pages7
JournalBlood
Volume87
Issue number10
StatePublished - May 15 1996

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Frameshift Mutation
Amyloidosis
Fibrinogen
Genes
Kidney
Polymorphism
Amyloid
Codon
Plasmas
Peptides
Polymerase chain reaction
DNA sequences
Amyloid Plaques
DNA Sequence Analysis
Restriction Fragment Length Polymorphisms
Conformations
Immune Sera
Siblings
Deposits
Nucleotides

ASJC Scopus subject areas

  • Hematology

Cite this

Uemichi, T., Liepnieks, J. J., Yamada, T., Gertz, M., Bang, N., & Benson, M. D. (1996). A frame shift mutation in the fibrinogen Aα chain gene in a kindred with renal amyloidosis. Blood, 87(10), 4197-4203.

A frame shift mutation in the fibrinogen Aα chain gene in a kindred with renal amyloidosis. / Uemichi, Tomoyuki; Liepnieks, Juris J.; Yamada, Toshiyuki; Gertz, Morie; Bang, Nils; Benson, Merrill D.

In: Blood, Vol. 87, No. 10, 15.05.1996, p. 4197-4203.

Research output: Contribution to journalArticle

Uemichi, T, Liepnieks, JJ, Yamada, T, Gertz, M, Bang, N & Benson, MD 1996, 'A frame shift mutation in the fibrinogen Aα chain gene in a kindred with renal amyloidosis', Blood, vol. 87, no. 10, pp. 4197-4203.
Uemichi T, Liepnieks JJ, Yamada T, Gertz M, Bang N, Benson MD. A frame shift mutation in the fibrinogen Aα chain gene in a kindred with renal amyloidosis. Blood. 1996 May 15;87(10):4197-4203.
Uemichi, Tomoyuki ; Liepnieks, Juris J. ; Yamada, Toshiyuki ; Gertz, Morie ; Bang, Nils ; Benson, Merrill D. / A frame shift mutation in the fibrinogen Aα chain gene in a kindred with renal amyloidosis. In: Blood. 1996 ; Vol. 87, No. 10. pp. 4197-4203.
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