THYROGLOBULIN EXON-10 GENE POINT MUTATION IN A PATIENT WITH ENDEMIC GOITER

Iodine deficiency is the most relevant etiologic factor in endemic goi ter. However, the fact that not all residents in the same area eventua lly develop goiter suggests that individual factors might also be invo lved in the etiology of endemic goiter. We have previously reported a point mutation in thyroglobulin exon 10 associated with nonendemic sim ple goiter. In an attempt to determine whether the mutation in thyrogl obulin exon 10 might be linked to endemic goiter, we studied the genom ic organization of thyroglobulin exon 10 in 36 patients diagnosed with endemic goiter by Southern blot, PCR, and sequencing analysis. We als o analyzed by Southern blot the organization of the genomic region tha t contains thyroglobulin exons 1 to 11. In one case, we observed a poi nt mutation in thyroglobulin exon 10. Sequencing analysis revealed a m utation at position 2610 of the cDNA, which implies a G to T substitut ion. This single base change results in a glutamine to histidine subst itution and is the same as that previously reported by our group in pa tients with nonendemic goiter. To our knowledge, this is the first tim e that a mutation in the thyroglobulin gene has been described in a pa tient with endemic simple goiter and further confirms the association between the exon 10 mutation and development of goiter.