title: Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism.
abstract: The thyrotropin receptor (TSHR), a member of the large family of G protein-coupled receptors, controls both the function and growth of thyroid cells via stimulation of adenylyl cyclase. We report two different mutations in the TSHR gene of affected members of two large pedigrees with non-autoimmune autosomal dominant hyperthyroidism (toxic thyroid hyperplasia), that involve residues in the third (Val509Ala) and seventh (Cys672Tyr) transmembrane segments. When expressed by transfection in COS-7 cells, the mutated receptors display a higher constitutive activation of adenylyl cyclase than wild type. This new disease entity is the germline counterpart of hyperfunctioning thyroid adenomas, in which different somatic mutations with similar functional characteristics have been demonstrated.
authors.affiliation: Institut de Recherche Interdisciplinaire, Faculty of Medicine, University of Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Duprez
authors.forename: J
authors.initials: J
authors.lastname: Parma
authors.forename: J
authors.initials: J
authors.lastname: Van Sande
authors.forename: A
authors.initials: A
authors.lastname: Allgeier
authors.forename: J
authors.initials: J
authors.lastname: Leclère
authors.forename: C
authors.initials: C
authors.lastname: Schvartz
authors.forename: M J
authors.initials: MJ
authors.lastname: Delisle
authors.forename: M
authors.initials: M
authors.lastname: Decoulx
authors.forename: J
authors.initials: J
authors.lastname: Orgiazzi
authors.forename: J
authors.initials: J
authors.lastname: Dumont
mesh_terms: D000236:Adenoma / Q000235:genetics; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000502:physiology; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D005260:Female; D005602:France / Q000453:epidemiology; D005799:Genes, Dominant; D006801:Humans; D006980:Hyperthyroidism / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D011487:Protein Conformation; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015290:Second Messenger Systems; D013964:Thyroid Neoplasms / Q000235:genetics; D014162:Transfection
chemical_list: D011989:Receptors, Thyrotropin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases