title: Haplotype analysis of familial amyloidotic polyneuropathy. Evidence for multiple origins of the Val----Met mutation most common to the disease.
abstract: Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant genetic disease characterized by systemic accumulation of amyloid fibrils. A major component of FAP amyloid 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.
authors.affiliation: Research Laboratory for Genetic Information, Kyushu University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: H
authors.initials: H
authors.lastname: Furuya
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: M J
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: P P
authors.initials: PP
authors.lastname: Costa
authors.forename: Y
authors.initials: Y
authors.lastname: Sakaki
mesh_terms: D006239:Haplotypes; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D007564:Japan; D009154:Mutation; D015345:Oligonucleotide Probes; D011174:Portugal; D011228:Prealbumin / Q000235:genetics*
chemical_list: D015345:Oligonucleotide Probes; D011228:Prealbumin