Haplotype analysis of familial amyloidotic polyneuropathy. Evidence for multiple origins of the Val----Met mutation most common to the disease.
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.
Yoshioka
K
K
Research Laboratory for Genetic Information, Kyushu University, Japan.
Furuya
H
H
Sasaki
H
H
Saraiva
M J
MJ
Costa
P P
PP
Sakaki
Y
Y
D006239:Haplotypes; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D007564:Japan; D009154:Mutation; D015345:Oligonucleotide Probes; D011174:Portugal; D011228:Prealbumin / Q000235:genetics*
D015345:Oligonucleotide Probes; D011228:Prealbumin