Taniyama M, Kusano S, Miyoshi Y, Nakamura H, Kaihara M, Tobe T, Tomita M, Katagiri T, Ban Y
Third Dept. of Internal Medicine, School of Medicine, Showa University (Tokyo), Japan.
Exp Clin Endocrinol Diabetes. 1996;104(4):339-43. doi: 10.1055/s-0029-1211464.
Recent studies have revealed mutations in the thyroid hormone receptor beta (TR beta) gene as a cause of the most cases of the thyroid hormone resistance syndrome. We have identified a novel nonsense mutation in codon 449 in the 3' end of exon 10 in the TR beta gene in a 16-year-old male patient with generalized resistance to thyroid hormone who also had familial thyroxine binding globulin deficiency. Receptor protein generated from this gene is thought to be 13 amino acid deficient at carboxy-terminus. Resistance to thyroid hormone was mild at least when the patient was evaluated. The patient was eumetabolic in the presence of elevated plasma-free thyroid hormone levels, and both thyrotrope and peripheral tissues responded to triiodothyronine (T3) administration. This mildness of resistance is in contrast to severe resistance to thyroid hormone in two previously reported cases with truncated receptors in which 16 amino acids or 11 amino acids were deficient at C-terminus. Thus, truncation of C-terminus of thyroid hormone receptor beta does not uniformly produce sever resistance.
最近的研究表明，甲状腺激素受体β（TRβ）基因突变是大多数甲状腺激素抵抗综合征病例的病因。我们在一名16岁男性甲状腺激素全身性抵抗患者的TRβ基因第10外显子3'端的449密码子中发现了一个新的无义突变，该患者还患有家族性甲状腺素结合球蛋白缺乏症。由该基因产生的受体蛋白被认为在羧基末端缺少13个氨基酸。至少在对该患者进行评估时，其对甲状腺激素的抵抗较轻。在血浆游离甲状腺激素水平升高的情况下，患者代谢正常，促甲状腺激素和外周组织对三碘甲状腺原氨酸（T3）给药均有反应。这种轻度抵抗与之前报道的两例受体截短的严重甲状腺激素抵抗病例形成对比，在这两例病例中，C末端分别缺少16个氨基酸或11个氨基酸。因此，甲状腺激素受体β的C末端截短并不一定会导致严重抵抗。
