title: Generalized resistance to thyroid hormone: identification of a novel c-erbA beta thyroid hormone receptor variant (Leu450) in a Japanese family and analysis of its secondary structure by the Chou and Fasman method.
abstract: Generalized resistance to thyroid hormone (GRTH) is characterized by elevated circulating levels of thyroid hormone in the presence of a eumetabolic state and failure to respond to triiodothyronine. Various point mutations in the c-erbA beta thyroid hormone receptor gene are known to be responsible for different phenotypes of GRTH. We herein report a new c-erbA beta variant in a Japanese family. The variant consisting of a cytosine to adenine base substitution at nucleotide position 1650 altered phenylalanine to leucine in codon 450 in the T3-binding domain of c-erbA beta. This base substitution was found in one allele of the 2 affected members of the family. The in vitro translation products of this mutant c-erbA beta gene demonstrated a significantly reduced T3-binding affinity. The secondary structure of this mutant thyroid hormone receptor predicted by the Chou and Fasman method included a new turn in the alpha helix structure in the T3-binding domain. We also discuss the secondary structures of the previously reported mutant receptors.
authors.affiliation: Department of Clinical Genetics, Kyushu University, Oita, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D005091:Exons / Q000235:genetics*; D005260:Female; D018776:Genes, erbA / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000235:genetics; D013960:Thyroid Function Tests; D018382:Thyroid Hormone Resistance Syndrome / Q000097:blood / Q000235:genetics*
chemical_list: D011988:Receptors, Thyroid Hormone