目的:对1例甲状腺激素抵抗综合征(RTH)先证者及其家系成员进行甲状腺激素受体β(TRβ)基因突变检测,并分析误诊情况.方法:取得先证者及家系成员知情同意后,收集RTH先证者及家系成员的临床资料,抽取先证者及其余10名家系成员的外周血抽提基因组DNA,应用PCR扩增TR β基因的3-10号外显子编码区并直接测序,分析家系成员误诊情况.结果:11名家族成员中共发现3名患者,DNA测序结果显示先证者及其儿子、母亲TR β第9外显子存在c.1234 A>G(p.A317T)错义突变,为杂合突变.先证者表现为心悸消瘦,先证者儿子表现为多动,先证者母亲症状不明显.先证者和其儿子因在外院被误诊甲状腺功能亢进症已行放射性碘治疗,需终身甲状腺激素替代,先证者母亲因症状隐匿未被误诊误治.结论:TRβ基因第9外显子c.1234 A>G突变是引起本家系RTH的原因,提高对该病的认识有助于避免不适当的治疗.%Objective: To investigate the molecular genetics in one patients with resistance to thyroid hor-mone (RTH) in the pedigree and to analyze her general signs and misdiagnosis. Methods: With written informed consents obtained, the clinical data of the female patient with RTH and her family members were collected. Genomic DNA was extracted from the peripheral blood samples of the patient and her ten family members. The exons 3-10 coding region of thyroid hormone receptor β(TRβ)genes were amplified by PCR,and then directly sequenced. Results: In this pedigree, there were three RTHβ patients. The analysis identified a heterozygous mutant at exon 9 of TRβ(c.1234 A>G),which led to missense mutation in the proband as well as in her son and her mother. The proband presented with palpitation and weight loss, while her son had the characteristics of hy-peractivity and the mother of the proband showed mild symptoms. Unfortunately, the proband and her son had been misdiagnosed for hyperthyroidism and underwent radioiodine therapy in another hospital. They may have to take levothyroxine for lifelong time. The mother of the proband had not been misdiagnosed because of the mild clinical manifestation.Conclusion:The RTH in the pedigree was caused by the TRβ mutation(A317T).It is of importance for doctors to know this disease better so that hormone ablation such as radioiodine therapy or thyroid surgery could be prevented.
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