title: TRα receptor mutations extend the spectrum of syndromes of reduced sensitivity to thyroid hormone.
abstract: Since 2012, eight different abnormalities have been described in the THRA gene (encoding the TRα1 thyroid hormone receptor) of 14 patients from 9 families. These mutations induce a clinical phenotype (resistance to thyroid hormone type α) associating symptoms of untreated mild congenital hypothyroidism and a near-normal range of free and total thyroid hormones and TSH (the T4/T3 ratio is nevertheless usually low). The phenotype can diversely include short stature (due to growth retardation), dysmorphic syndrome (face and limb extremities), psychoneuromotor disorders, constipation and bradycardia. The identified genetic abnormalities are located within the ligand-binding domain and result in defective T3 binding, an abnormally strong interaction with corepressors and a dominant negative activity against still functional receptors. The identification of patients with consistent phenotypes and the underlying mutations are warranted to better delineate the spectrum of the syndromes of reduced sensitivity to thyroid hormone.
authors.affiliation: Hospices civils de Lyon, centre hospitalier Lyon Sud, service de biochimie biologie moléculaire Sud, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; Université Lyon 1, faculté de médecine Lyon Est, centre Léon-Bérard, centre de recherche en cancérologie de Lyon, Inserm 1052 CNRS 5286, 69373 Lyon cedex 08, France. Electronic address: virginie.vlaeminck-guillem@univ-lyon1.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Vlaeminck-Guillem
authors.affiliation: CHRU de Lille, hôpital Huriez, service d'endocrinologie et métabolisme, 59000 Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Espiard
authors.affiliation: Université de Lyon, CNRS, Inra, université Claude-Bernard Lyon 1, École normale supérieure de Lyon, Institut de génomique fonctionnelle de Lyon, 69007 Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
authors.affiliation: CHRU de Lille, hôpital Huriez, service d'endocrinologie et métabolisme, 59000 Lille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Wémeau
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001919:Bradycardia / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D004392:Dwarfism / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D011596:Psychomotor Disorders / Q000235:genetics; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics* / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000378:metabolism; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin