Resistance to thyroid hormone syndrome due to p.Cys446Ser variant of THRbeta gene in a pedigree.
10.3760/cma.j.cn511374-20200619-00457
- VernacularTitle:THRβ基因p.Cys446Ser变异导致甲状腺激素抵抗综合征一家系
- Author:
Shuguo SUN
1
;
Yuanhong DING
;
Yan KONG
;
Fanxiang WANG
Author Information
1. Department of Endocrinology, Rizhao Central Hospital, Rizhao, Shandong 276800, China. rizhao2008@163.com.
- Publication Type:Journal Article
- MeSH:
Female;
Genomics;
Heterozygote;
Humans;
Mothers;
Mutation;
Pedigree
- From:
Chinese Journal of Medical Genetics
2021;38(9):838-840
- CountryChina
- Language:Chinese
-
Abstract:
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.
