Familial amyloid polyneuropathy: Alanine‐for‐threonine substitution in the transthyretin (prealbumin) molecule

Arnulf H. Koeppen, Margaret R. Wallace, Merrill D. Benson, Klaus Altland

Research output: Contribution to journalArticle

11 Scopus citations


A previously reported family with amyloid polyneuropathy (FAP) was reinvestigated to determine the type of mutation in the transthyretin (prealbumin) molecule. Transthyretin was isolated from amyloid‐laden myocardium and serum, and tryptic peptides were resolved by high‐performance liquid chromatography. Amino acid sequencing of an anomalous peptide revealed an alanine‐for‐threonine substitution corresponding to position No. 60 of the transthyretin monomer. Detection of the FAP gene in asymptomatic carriers was accomplished by hybrid isoelectric focusing of transthyretin in the presence of dithiothreitol and high concentrations of urea, and by Southern blotting of Pvull‐digested leukocyte deoxyribonucleic acid. This type of FAP was found to be identical to the previously described Appalachian amyloid. Patients with FAP and their asymptomatic gene‐carrying offspring had significantly reduced levels of serum transthyretin and retinol‐binding protein.

Original languageEnglish (US)
Pages (from-to)1065-1075
Number of pages11
JournalMuscle & Nerve
Issue number11
StatePublished - Nov 1990


  • Southern blot
  • high‐performance liquid chromatography
  • mutation
  • retinol‐binding protein
  • transthyretin

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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