四个巴西甲状腺激素抵抗家系的临床特征与基因分析

Clinical features and genetic analysis of four Brazilian kindreds with resistance to thyroid hormone.

作者信息

Magalhães Patricia Künzle Ribeiro, Rodrigues Dare Gustavo Leopoldo, Rodrigues Dos Santos Sandra, Nogueira Celia Regina, de Castro Margaret, Zanini Maciel Lea Maria

机构信息

Division of Endocrinology, Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.

出版信息

Clin Endocrinol (Oxf). 2007 Nov;67(5):748-53. doi: 10.1111/j.1365-2265.2007.02956.x. Epub 2007 Jul 4.

DOI:10.1111/j.1365-2265.2007.02956.x

PMID:17610520

Abstract

OBJECTIVE

Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone usually due to mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor beta (TRbeta). In the present report we describe the clinical and laboratory characteristics and the genetic analysis of patients with this rare disorder from a Brazilian population.

PATIENTS

Four unrelated Brazilian families with diagnosis of RTH were studied. Age at diagnosis varied from 14 months to 29 years.

RESULTS

All affected individuals were clinically euthyroid, except for one patient who presented immediately after birth with hyperthyroidism. All individuals had tachycardia and goitre, elevated concentrations of free thyroid hormones and reduced sensitivity to thyroid hormone. Direct sequencing analysis of the TRbeta gene revealed four previously reported mutations: c.949G-->A, c.1313G-->A, c.1357C-->A and c.1358dupC in families A, B, C and D, respectively.

CONCLUSION

The present report shows that the frequent mutations described in the thyroid hormone receptor worldwide are also present in the Brazilian population, which is characterized by a variable ethnic background.

摘要

目的

甲状腺激素抵抗（RTH）是一种常染色体显性遗传综合征，其特征为组织对甲状腺激素的反应性降低，通常是由于甲状腺激素受体β（TRβ）的配体结合域及相邻铰链区发生突变所致。在本报告中，我们描述了来自巴西人群的患有这种罕见疾病的患者的临床和实验室特征以及基因分析情况。

患者

对4个诊断为RTH的非血缘关系的巴西家庭进行了研究。诊断时的年龄从14个月到29岁不等。

结果

除1例出生后即表现为甲状腺功能亢进的患者外，所有受影响个体临床甲状腺功能均正常。所有个体均有心动过速和甲状腺肿大，游离甲状腺激素浓度升高且对甲状腺激素的敏感性降低。对TRβ基因进行直接测序分析发现了4个先前报道的突变：在A、B、C和D家庭中分别为c.949G→A、c.1313G→A、c.1357C→A和c.1358dupC。