Analysis of the TSH receptor gene structure in various thyroid disorders: DNA from thyroid adenomas can have large...

We examined the structure of the TSH receptor gene in various thyroid disorders by a restriction fragment length polymorphism (RFLP) study with a cloned human TSH receptor cDNA as a probe. Southern blot analysis of DNAs in peripheral white blood cells obtained from normal individuals revealed a single band in each of several restriction enzyme digestions, indicating that the TSH receptor gene is a single copy gene in the human genome. Although RFLPs were not detected in peripheral blood cells and thyroid tissues in patients with Graves' disease, thyroid carcinomas, or subacute thyroiditis, significant RFLPs were found in 2 of 6 patients with adenoma in all restriction enzyme digestions examined. Moreover, these RFLPs were heterozygous and adenoma specific, and these additional bands in adenoma were amplified in both cases. We conclude that there are no major abnormalities in the structure of the TSH receptor gene in patients with Graves' disease, thyroid carcinoma, or subacute thyroiditis, although there may be a possibility of point mutations, small insertions, or deletions that cannot be detected by RFLP studies, and that there are large insertions or deletions in the region, including the TSH receptor gene, in some patients with thyroid adenoma.