ClinVar

In affected members of a large kindred from northern France with autosomal dominant nonautoimmune hyperthyroidism (609152) originally reported by Thomas et al. (1982), Duprez et al. (1994) identified a heterozygous T-to-C transition in exon 10 of the TSHR gene, resulting in a val509-to-ala (V509A) substitution in the third transmembrane domain of the protein. Functional expression studies of the V509A mutation showed higher basal intracellular cAMP levels with high constitutive activation of the receptor. Duprez et al. (1994) noted that autosomal dominant nonautoimmune hyperthyroidism is the germline counterpart of hyperfunctioning thyroid adenomas (e.g., 603372.0017), in which different somatic mutations with similar functional characteristics have been demonstrated.