title: Three new mutations of thyroid hormone receptor-beta associated with resistance to thyroid hormone.
abstract: Three novel point mutations at nucleotides 1249, 1282, and 1614 (exons 9 and 10) of the human thyroid hormone receptor-beta gene were observed in six individuals affected by the syndrome of resistance to thyroid hormone. All three mutations occurred in a heterozygous pattern and caused the following changes in the mature form of the receptor protein: Asp322 to Asn, Glu333 to Gln, and Lys443 to Asn, respectively. The first and third point mutations arose in two unrelated families from eastern Sicily, whereas the second concerned an individual from southern Calabria, apparently presenting a sporadic form of the resistance syndrome. The clinical and biochemical features of resistance to thyroid hormone, both before and after the administration of thyroid hormones, highlight the striking intrafamilial heterogeneity in the phenotypical presentation of the syndrome.
authors.affiliation: Institute of Endocrinology, University of Messina, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bartolone
authors.forename: C
authors.initials: C
authors.lastname: Regalbuto
authors.forename: S
authors.initials: S
authors.lastname: Benvenga
authors.forename: S
authors.initials: S
authors.lastname: Filetti
authors.forename: F
authors.initials: F
authors.lastname: Trimarchi
authors.forename: A
authors.initials: A
authors.lastname: Pontecorvi
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001483:Base Sequence; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005971:Glutamates / Q000235:genetics; D018698:Glutamic Acid; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics*; D012802:Sicily; D013577:Syndrome; D013963:Thyroid Hormones / Q000494:pharmacology*
chemical_list: D005971:Glutamates; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D001216:Asparagine; D008239:Lysine