甲状腺激素受体β基因A317T杂合突变致垂体甲状腺激素抵抗综合征家系分析  

Pedigree analysis of a pituitary-resistance to thyroid hormone syndrome family caused by heterozygous A317T mutation in thyroid hormone receptor β gene

作　　者：汪保安[1] 王敏[2] 陆菊明[1] 母义明[1] 郭清华[1] 吕朝晖[1] 

机构地区：[1]解放军总医院内分泌科,北京100853 [2]解放军总医院健康管理研究院国宾三科,北京100853

出　　处：《中华内分泌代谢杂志》2017年第3期215-219,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金（81570705、81270866）

摘　　要：分析-选择性垂体甲状腺激素抵抗综合征家系临床特征及其甲状腺激素受体B（THRβ）基因的突变情况。收集患者、妹妹及其父母和4名母系亲属的临床资料，并采集外周血标本，分离白细胞．提取基因组DNA；以化学发光免疫分析法检测血清甲状腺激素水平，以PCR分别扩增THRβ基因的10个外显子并测序分析。此家系中先证者及其母亲有心悸、怕热多汗等甲状腺功能亢进症状，其母有房颤，其余家庭成员无甲状腺功能亢进和甲状腺功能减退临床表现。测序发现患者THRβ基因9号外显子存在第949位核苷酸G转换为A的杂合错义突变，导致THRβ基因编码的第317位氨基酸由丙氨酸变为苏氨酸（A317T）；患者母亲也具有相同的杂合突变，而患者其他亲属未发现此突变。该家系中先证者及其母亲有垂体甲状腺激素抵抗的临床表现，基因测序证实两者均存在THRβ基因A317T杂合突变，而其他成员没有。该突变位点是在中国患者中首次报道的突变类型。To study thyroid hormone receptor β（ THRβ） gene mutation in a pituitary-resistance to thyroid hormone syndrome family. The peripheral blood samples of the patient, his sister, parents, and 4 maternal relatives were collected. Then serum was isolated for detecting thyroid hormone levels with chemiluminescence immunoassay, and DNA was extracted for PCR, and 10 exons of THRβ gene were sequenced. The patient and his mother had the hyperthyroid symptom for many years and his mother with atrial fibrillation. The G-A heterozygous transition mutation was confirmed by exon sequencing at nucleotide 949 within exon 9 of THRβ gene in the patient and his mother, which was a missense mutation causing a substitution of Alanine to Threonine （A317T）. No mutation was found in THRβ gene in other family members. This is the first Chinese family reported with pituitary thyroid hormone resistance syndrome caused by a A317T mutation in the thyroid hormone receptor β gene.

关 键 词：甲状腺激素抵抗综合征 垂体甲状腺激素抵抗综合征 甲状腺激素受体β 基因突变 中国人 

分 类 号：R581[医药卫生—内分泌]