Identification of the circulating amyloid precursor and other gelsolin metabolites in patients with G654A mutation in the gelsolin gene (Finnish familial amyloidosis): pathogenetic and diagnostic implications

Lab Invest. 1997 Oct;77(4):299-304.


Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant type of systemic amyloidosis caused by a G654A (Asn-187) or G654T (Tyr-187) mutation in the gelsolin gene. Herein we show that patients with the Asn-187 gelsolin mutation have, in addition to full-sized gelsolin, a series of lower-Mr C-terminal fragments of gelsolin (Mr of 70,000-45,000) in the circulation, and that a 50 to 55-kd fragment of gelsolin is excreted in the urine. In homozygous FAF (Asn-187), the 65-kd fragment, which contains the amyloid-forming region (Ala173-Met243), and the 55-kd fragment, which is devoid of that region, are the major gelsolin species in plasma; whereas normal gelsolin, as well as a 70-kd fragment identified as the C-terminal portion of gelsolin starting at Glu122, and a 45-kd fragment starting at Ser384, are minor components. In patients heterozygous for the Asn-187 mutation--the usual form of the expression of the dominant disease--normal-sized gelsolin is the major circulating form; the 65- and 55-kd fragments represent minor components. Immunodetection of the plasma 65-kd gelsolin fragment, which is disease-specific, and measurement of the urinary gelsolin fragment provide useful means for diagnosing FAF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / blood*
  • Amyloidosis / genetics*
  • Antibodies, Monoclonal
  • Blotting, Western
  • Chromatography, Affinity
  • Gelsolin / genetics*
  • Gelsolin / metabolism
  • Heterozygote
  • Homozygote
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Mutation


  • Amyloid beta-Protein Precursor
  • Antibodies, Monoclonal
  • Gelsolin