甲状腺激素受体 基因第10外显子H435L突变致甲状腺激素抵抗并桥本甲状腺炎

基础医学与临床 ›› 2009, Vol. 29 ›› Issue (9): 974-978.

甲状腺激素受体基因第10外显子H435L突变致甲状腺激素抵抗并桥本甲状腺炎

连小兰聂敏白耀

中国医学科学院北京协和医学院北京协和医院内分泌科

收稿日期:2009-07-02 修回日期:2009-07-14 出版日期:2009-09-20 发布日期:2009-09-20
通讯作者: 连小兰

Thyroid hormone resistance with H435L mutation in exon 10 of thyroid hormone receptor gene associated with Hashimoto's thyroiditis

Xiao-lan LIAN, Min NIE, Yao BAI

Dept.of Endocrinology, PUMC hospital, CAMS & PUMC

Received:2009-07-02 Revised:2009-07-14 Online:2009-09-20 Published:2009-09-20
Contact: Xiao-lan LIAN,

摘要/Abstract

摘要： 目的研究甲状腺激素抵抗（RTH）合并桥本甲状腺炎（HT）患儿临床特点和甲状腺激素受体基因（TR ）突变类型。方法对1例7岁男性RTH合并HT患儿临床特点进行分析，同时，用PCR法扩增患儿及双亲外周血DNA的TR 第5～10外显子，序列比对。结果患儿TRβ第10外显子第1304位碱基发生杂合错义点突变，A 替换成T （c. 1304 A > T），致第435位密码子从CAT变成了CTT，对应的组氨酸被亮氨酸所替代，导致RTH。随诊中新发HT。结论 TR 第10外显子H435L突变导致RTH；同时，持续RTH可能引发HT。

关键词: 甲状腺激素受体β基因, 甲状腺激素抵抗, 桥本甲状腺炎

Abstract: Objective To study mutations of thyroid hormone receptor β gene (TRβ) and clinical characteristics of a patient with resistance to thyroid hormone (RTH) associated with Hashimoto's thyroiditis (HT). Methods clinical manifestations were observed in a 7-year-old boy with RTH. Meantime, genomic DNA was extracted from peripheral blood of the patient and his parents. exons 5～10 of TRβ gene were amplified by PCR and sequenced directly. Results A heterozygote point mutation in exon 10 of TRβ was identified in the patient, which is a A to T transition in nucleotide 1403（c. 1304 A > T）, resulting in His to Leu ( CAT→CTT) substituted at codon 435 ( H435L). No mutation was identified in the patient's parents. HT occurred in the patient during following-up. Conclusion H435L mutation in exon 10 of TRβ gene leads to resistance to thyroid hormone. Meanwhile, consistent RTH might lead to HT.

Key words: thyroid hormone receptor β gene, resistance to thyroid hormone, Hashimoto’s thyroiditis

连小兰聂敏白耀. 甲状腺激素受体基因第10外显子H435L突变致甲状腺激素抵抗并桥本甲状腺炎[J]. 基础医学与临床, 2009, 29(9): 974-978.

Xiao-lan LIAN; Min NIE; Yao BAI. Thyroid hormone resistance with H435L mutation in exon 10 of thyroid hormone receptor gene associated with Hashimoto's thyroiditis[J]. Basic & Clinical Medicine, 2009, 29(9): 974-978.