Haplotype Analisis of Familial Amyloidotic Polyneuropathy: an Evidence for Multiple Origins of the Val→met Mutation

  • Katsuji Yoshioka
  • Hirokazu Furuya
  • Hiroyuki Sasaki
  • Maria Joao Mascarenhas Saraiva
  • Pedro P. Costa
  • Yoshiyuki Sakaki


The variant of transthyretin (TTR, also called prealbumin) has been identified as a major component of amyloid fibrils of familial amyloidotic polyneuropathy (FAP). In particular, the variant with30 Val→Met substitution has been commonly found in FAP of various ethnic groups. To understand the origin and spread of the Val→Met mutation, we have analyzed DNA polymorphisms associated with the TTR gene in six Japanese FAP families and several Portuguese FAP patients. Three distinct haplotypes associated with the Val→Met mutation were identified in Japanese FAP families, one of which was also found in Portuguese patients. Nucleotide sequence analysis revealed that the Val→Met mutation is caused by a C-T transition at a CpG dinucleotide sequence of mutation hotspot on the anti-sense strand of TTR gene DNA. These results suggest that the Val→Met mutation has frequently recurred in human population to generate FAP families in various ethnic groups.


Amyloid Fibril Sodium Lauryl Sulfate Nucleotide Sequence Analysis Distinct Haplotype Familial Amyloidotic Polyneuropathy 
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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Katsuji Yoshioka
    • 1
  • Hirokazu Furuya
    • 1
  • Hiroyuki Sasaki
    • 1
  • Maria Joao Mascarenhas Saraiva
    • 2
  • Pedro P. Costa
    • 2
  • Yoshiyuki Sakaki
    • 1
  1. 1.Research Laboratory for Genetic InformationKyushu University 18Maidashi, Fukuoka 812Japan
  2. 2.Instituto Nacional de Saude, Centro de Estudos de ParamiloidoseHospital de Sto. AntonioPortoPortugal

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