Summary
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-erbAβ thyroid hormone receptor gene are known to be responsible for different phenotypes of GRTH. We herein report a new c-erbAβ 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-erbAβ. This base substitution was found in one allele of the 2 affected members of the family. Thein vitro translation products of this mutant c-erbAβ 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 α helix structure in the T3-binding domain. We also discuss the secondary structures of the previously reported mutant receptors.
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Hiramatsu, R., Abe, M., Morita, M. et al. Generalized resistance to thyroid hormone: Identification of a novel c-erbAβ thyroid hormone receptor variant (leu450) in a Japanese family and analysis of its secondary structure by the Chou and Fasman method. Jap J Human Genet 39, 365–377 (1994). https://doi.org/10.1007/BF01892382
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DOI: https://doi.org/10.1007/BF01892382