Clinical significance of the combined screening of thyroid stimulating hormone and candidate genes for congenital hypothy-roidism
10.13602/j.cnki.jcls.2025.07.02
- VernacularTitle:促甲状腺激素和候选基因联合筛查先天性甲状腺功能减低症的临床意义
- Author:
Yahong LI
1
;
Yun SUN
1
;
Xin WANG
1
;
Xianwei GUAN
1
;
Peiying YANG
1
;
Tao JIANG
1
;
Zhengfeng XU
1
Author Information
1. 南京医科大学附属妇产医院&南京市妇幼保健院遗传医学中心,南京 210004
- Publication Type:Journal Article
- Keywords:
congenital hypothyroidism;
newborn screening;
genetic screening;
gene variation
- From:
Chinese Journal of Clinical Laboratory Science
2025;43(7):488-494
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical significance of the combined screening of thyroid stimulating hormone(TSH)and seven candidate pathogenic genes of congenital hypothyroidism(CH)for CH.Methods 16 645 newborns delivered in Nanjing Women and Children's Healthcare Hospital from July 2022 to July 2023 were performed the screening of TSH.Their DNA was extracted from dried blood spots and the chip capture second-generation sequencing technology was used to detect the candidate pathogenic genes,in-cluding dual oxidase 2(DUOX2),dual oxidase maturation factor 2(DUOXA2),prophet of pit-1(PROP1),thyroid-stimulating hor-mone receptor(TSHR),thyroid peroxidase(TPO),thyroglobulin(TG),and paired box 8(PAX8).The sensitivity,specificity,pos-itive predictive value(PPV),and negative predictive value(NPV)of the screening of TSH,candidate genes,and their combination for CH were analyzed.Results A total of 13 CH patients were screened out based on sensitive thyroid stimulating hormone(sTSH)and free thyroxine(FT4),including 3 patients with hyperthyrotropinemia.Among them,11 were screened out by TSH alone,4 were screened out by candidate genes alone,and 2 were screened out by the combination of TSH and candidate genes.The sensitivity,speci-ficity,PPV,and NPV of TSH for screening CH were 84.62％,99.23％,7.91％,and 99.97％,respectively.The sensitivity,specifici-ty,PPV,and NPV of candidate genes for screening CH were 30.77％,99.87％,15.38％,and 99.87％,respectively.The sensitivity,specificity,PPV,and NPV of the combination of TSH and candidate genes for screening CH were 100％,99.09％,7.88％,and 100％,respectively.The primary mutant gene in the samples with positive candidate genes was DUOX2(85.71％),mainly point muta-tions,among which the c.1588A>T variant was the most common(16.67％).PAX8(14.29％)was the second most common variation,and all of the variation point were c.280G>A.No positive samples for the pathogenic variants of DUOXA2,TSHR,PROP1,TPO,and TG were detected.Conclusion The combined screening of TSH and candidate genes helps to improve the screening efficacy of CH.The genetic etiology of CH in Nanjing area may be mainly the variation of DUOX2 and PAX8 genes.
