From gene to disease; thyroid stimulating hormone receptor, hyperthyroidism and hypothyroidism
Wiersinga, W.M.
Nederlands Tijdschrift Voor Geneeskunde 145(18): 869-871
2001
ISSN/ISBN: 0028-2162 PMID: 11379397 Document Number: 539183
The thyroid-stimulating hormone receptor (TSH-R) gene appears to be very sensitive to mutagenesis, in view of the vast number of reported mutations. Loss-of-function germline mutations occur preferentially in the hormone-binding extracellular domain of the TSH-R, resulting in familial TSH resistance. Gain-of-function germline mutations occur preferentially in the transmembrane domain of the TSH-R, resulting in familial non-autoimmune hyperthyroidism. Familial gestational hyperthyroidism is due to a mutant TSH-R which is hypersensitive to chorionic gonadotropin. Somatic gain-of-function mutations are a major cause of toxic thyroid adenomas.