Hiramatsu R, Abe M, Morita M, Noguchi S, Suzuki T
Department of Clinical Genetics, Kyushu University, Oita, Japan.
Jpn J Hum Genet. 1994 Dec;39(4):365-77. doi: 10.1007/BF01892382.
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.
全身性甲状腺激素抵抗（GRTH）的特征是在代谢正常的状态下循环甲状腺激素水平升高，且对三碘甲状腺原氨酸无反应。已知c-erbAβ甲状腺激素受体基因中的各种点突变是导致GRTH不同表型的原因。我们在此报告一个日本家族中的一种新的c-erbAβ变体。该变体由核苷酸位置1650处的胞嘧啶到腺嘌呤碱基替换组成，导致c-erbAβ的T3结合域中第450密码子的苯丙氨酸变为亮氨酸。在该家族的2名受影响成员的一个等位基因中发现了这种碱基替换。该突变c-erbAβ基因的体外翻译产物显示出显著降低的T3结合亲和力。用Chou和Fasman方法预测的这种突变甲状腺激素受体的二级结构在T3结合域的α螺旋结构中包括一个新的转角。我们还讨论了先前报道的突变受体的二级结构。
