Clinical, biochemical characteristics and genotype-phenotype analysis of congenital hypothyroidism diagnosed by newborn screening in China.
Agenesis
Congenital hypothyroidism
Digenic variants
Genotype and phenotype analysis
Goiter
Journal
Clinica chimica acta; international journal of clinical chemistry
ISSN: 1873-3492
Titre abrégé: Clin Chim Acta
Pays: Netherlands
ID NLM: 1302422
Informations de publication
Date de publication:
01 Jul 2023
01 Jul 2023
Historique:
received:
09
06
2023
revised:
23
06
2023
accepted:
27
06
2023
medline:
10
7
2023
pubmed:
1
7
2023
entrez:
30
6
2023
Statut:
ppublish
Résumé
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder worldwide. However, the underlying etiology remains unclear in most patients. The newborn screening was performed for TSH in dried blood spots. Serum TSH, T3, T4, free T3(FT3) and free T4 (FT4) were detected for the recalled children. High-throughput sequencing were applied to detect 29 known CH genes. The statistical analyses were performed to analyze the differences between biochemical data, thyroid volume, clinical prognosis and genetic results for 97 patients who had one or more variants in CH related genes. DUOX2 gene had the highest variant rate, followed by TG, TPO and TSHR gene. The "DUOX2 biallelic variants" group was associated with "Goiter", while "DUOX2 monoallelic variants" group was associated with "Agenesis". In addition, the TSH levels and initial L-T4 dose were significantly higher in "TPO biallelic variants" group than those in "DUOX2 and TSHR biallelic variants" groups. Our study showed dyshormonogenesis (DH) might be the leading pathophysiology of CH in Chinese populations. DUOX2 gene mostly caused goiter, but also could be associated with hypoplasia. TPO might play a more irreplaceable role than DUOX2. The digenic variants combination indicated the complexity of genetic etiology in CH.
Sections du résumé
BACKGROUND
BACKGROUND
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder worldwide. However, the underlying etiology remains unclear in most patients.
METHODS
METHODS
The newborn screening was performed for TSH in dried blood spots. Serum TSH, T3, T4, free T3(FT3) and free T4 (FT4) were detected for the recalled children. High-throughput sequencing were applied to detect 29 known CH genes. The statistical analyses were performed to analyze the differences between biochemical data, thyroid volume, clinical prognosis and genetic results for 97 patients who had one or more variants in CH related genes.
RESULTS
RESULTS
DUOX2 gene had the highest variant rate, followed by TG, TPO and TSHR gene. The "DUOX2 biallelic variants" group was associated with "Goiter", while "DUOX2 monoallelic variants" group was associated with "Agenesis". In addition, the TSH levels and initial L-T4 dose were significantly higher in "TPO biallelic variants" group than those in "DUOX2 and TSHR biallelic variants" groups.
CONCLUSIONS
CONCLUSIONS
Our study showed dyshormonogenesis (DH) might be the leading pathophysiology of CH in Chinese populations. DUOX2 gene mostly caused goiter, but also could be associated with hypoplasia. TPO might play a more irreplaceable role than DUOX2. The digenic variants combination indicated the complexity of genetic etiology in CH.
Identifiants
pubmed: 37390946
pii: S0009-8981(23)00261-9
doi: 10.1016/j.cca.2023.117459
pii:
doi:
Substances chimiques
Dual Oxidases
EC 1.11.1.-
Thyrotropin
9002-71-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
117459Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.