[一个家系中由于甲状腺激素受体β基因p.Cys446Ser变异导致的甲状腺激素抵抗综合征]
[Resistance to thyroid hormone syndrome due to p.Cys446Ser variant of THRbeta gene in a pedigree].
作者信息
Sun Shuguo, Ding Yuanhong, Kong Yan, Wang Fanxiang
机构信息
Department of Endocrinology, Rizhao Central Hospital, Rizhao, Shandong 276800, China.
出版信息
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Sep 10;38(9):838-840. doi: 10.3760/cma.j.cn511374-20200619-00457.
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 THRbeta gene were sequenced for the proband and members of his pedigree.
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 the THRbeta gene, which resulted in 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 THRbeta gene was predicted to be lilely pathogenic(PM1+PM2+PM5+PP3).
CONCLUSION
The c.1336T>A variant, identified in the exon 10 of the THRbeta gene, probably underlay the RTH in this pedigree. Genetic testing has validated the clinical diagnosis for this pedigree.
目的
探究一个患有甲状腺激素抵抗综合征（RTH）的中国家系的遗传基础。
方法
对先证者及其家系成员的甲状腺激素β受体（THRbeta）基因外显子7至10进行测序。
结果
该家系中鉴定出3例患者。所有患者均有心悸、乏力、甲状腺肿大、游离甲状腺激素和游离三碘甲状腺原氨酸升高，促甲状腺激素正常或升高。基因检测显示，先证者、其母亲、二姐及其一个女儿携带THRbeta基因杂合性c.1336T>A变异，该变异导致第446位的半胱氨酸被丝氨酸替代。该变异此前未见报道。根据美国医学遗传学与基因组学学会的标准和指南，THRbeta基因的c.1336T>A（p.Cys446Ser）变异预计可能致病（PM1+PM2+PM5+PP3）。
结论
在THRbeta基因外显子10中鉴定出的c.1336T>A变异可能是该家系RTH的病因。基因检测验证了该家系的临床诊断。
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