Haplotype analysis of familial amyloidotic polyneuropathy - Evidence for multiple origins of the Val→Met mutation most common to the disease

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

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant genetic disease characterized by systemic accumulation of amyloid fibrils. A major component of FAP anyloid has been identified as variant transthyretin (TTR, also called prealbumin). In particular, a variant with the substitution 30Val→Met has been commonly found in FAP of various ethnic groups. To understand the origin and spread of the Val→Met mutation, we 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. On the other hand, it was found that the Val→Met mutation can be explained by a C-T transition at the CpG dinucleotide sequence of a mutation hot spot. Thus, our findings indicate that the Val→Met mutation has probably recurred in the human population, to generate FAP families of independent origin.

Original languageEnglish
Pages (from-to)9-13
Number of pages5
JournalHuman Genetics
Volume82
Issue number1
DOIs
Publication statusPublished - Apr 1 1989

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Haplotype analysis of familial amyloidotic polyneuropathy - Evidence for multiple origins of the Val→Met mutation most common to the disease'. Together they form a unique fingerprint.

Cite this