| Research Abstract |
We identified 37 different thyroglobulin mutations (6 splice site mutations, 4 nonsense mutations, 1 single nucleotide deletion, and 26 missense mutations) in 71 cases form 71 families in Japan. These numbers are about 3 times of the cases reported in other countries. Among them four mutations C1058R, C1245R, C1588F, and C1977S are frequently found in Japan. The patients with the mutation C1058R, C1588F, and C1977S were found only in restricted areas in Western Japan, whereas the patients with the mutation C1245R were found all over Japan. In this study, we used a haplotype analysis to study if these mutations are due to founder effects or de novo mutations. First, we determined a haplotype of these patients in 11 different single nucleotide polymorphisms in the coding region of the thyroglobulin gene and then calculated occurrence of each haplotype according to the frequency of each allele in the general Japanese population. We found that 8 patients with the C1058R mutation, 4 patients with the C1588F mutation, and 9 patients with the C 1977S mutation each had the same haplotype in homozygosity and the occurrence of these haplotypes are 1:800, 000, 000, 1:150, 000, 000, and 1:37, 000, 000, 000, respectively, confirming that these mutations are due to founder effects. On the contrary, 3 patients out of 12 patients with the C1245R mutation had different haplotypes, suggesting that some of the C1245R mutations are de novo mutations.
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