Familial amyloidosis, Finnish type: G654----a mutation of the gelsolin gene in Finnish families and an unrelated American family

Genomics. 1992 Jul;13(3):898-901. doi: 10.1016/0888-7543(92)90182-r.

Abstract

The Finnish type of familial amyloid polyneuropathy (FAF) is an autosomal dominant form of systemic amyloidosis caused by a mutation in the gelsolin gene. The mutation leads to the expression of amyloidogenic mutant Asp187----Asn gelsolin, an actin-modulating protein. We previously developed a DNA test based on amplification by the polymerase chain reaction followed by allele-specific oligonucleotide hybridization that identifies the base substitution adenine for guanine at nucleotide 654 in the gelsolin gene causing the disease. We show here that the same mutation is present in members of six apparently unrelated Finnish families and in a member of an unrelated American family. These results, taken together with previously published findings in nine additional Finnish families and another unrelated American family, indicate that most, perhaps all, FAF patients in Finland and possibly worldwide carry the same mutation. We suggest two alternative explanations: (i) the mutation arose in a very early common ancestor or (ii) the Asn187 mutation is particularly, perhaps uniquely, amyloidogenic.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloidosis / genetics*
  • Calcium-Binding Proteins / genetics*
  • DNA Mutational Analysis
  • Female
  • Finland
  • Gelsolin
  • Humans
  • Male
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Pedigree
  • United States

Substances

  • Calcium-Binding Proteins
  • Gelsolin
  • Microfilament Proteins