Van gen naar ziekte; receptor voor thyreoïdstimulerend hormoon, hyper- en hypothyreoïdie

- 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.