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目的:对1个甲状腺激素抵抗综合征(resistance to thyroid hormone syndrome，RTH)家系进行基因变异分析，明确其可能的致病原因，为临床诊断提供依据。方法:对先证者及其家系成员n THRβ基因的第7~10外显子编码区进行测序。n 结果:3例RTH患者均表现为心慌、乏力和甲状腺肿大，游离甲状腺激素、游离三碘甲状腺原氨酸水平升高，而促甲状腺素正常或升高。基因检测结果显示先证者及其母亲、二姐和二姐的一女的n THRβ基因均存在c.1336T>A杂合变异，导致其编码的第446位半胱氨酸被丝氨酸所替代，为未报道过的新变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，n THRβ基因c.1336T>A(p.Cys446Ser)变异判定为可能致病性变异(PM1+PM2+PM5+PP3)。n 结论:THRβ基因第10外显子c.1336 T>A变异可能是引起本家系RTH的原因，基因检测结果为临床诊断提供了依据。n “,”Objective:To explore the genetic basis for a Chinese pedigree affected with resistance to thyroid hormone syndrome (RTH).Methods:Exons 7 to 10 of the n THRβ gene were sequenced for the proband and members of his pedigree.n Results:Three patients from the pedigree were identified. All have presented with palpitation, fatigue, goiter, elevated free thyroid hormone and free triiodothyronine, and normal or elevated thyrotropin. Genetic testing revealed that the proband, his mother, second sister and one of her daughters had carried a heterozygous c. 1336T>A variant of then THRβ gene, which resulted substitution of Cysteine by Serine at position 446. The variant was unreported previously. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c. 1336T>A(p.Cys446Ser)variant of THRβ gene was predicted to be lilely pathogenic(PM1+ PM2+ PM5+ PP3).n Conclusion:The c. 1336 T>A variant, identified in the exon 10 of then THRβ gene, probably underlay the RTH in this pedigree. Genetic testing has validated the clinical diagnosis for this pedigree.n