Functional analysis of thyroid peroxidase gene mutations resulting in congenital hypothyroidism.
TPO activity
bioinformatic analysis
congenital hypothyroidism
gene mutation
thyroid peroxidase
Journal
Clinical endocrinology
ISSN: 1365-2265
Titre abrégé: Clin Endocrinol (Oxf)
Pays: England
ID NLM: 0346653
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
12
09
2019
revised:
30
04
2020
accepted:
02
05
2020
pubmed:
20
5
2020
medline:
19
8
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
Thyroid peroxidase (TPO) is essential for thyroid hormone biosynthesis. TPO mutations might lead to congenital hypothyroidism. In the present study, we analysed the function of a compound heterozygous TPO mutation in a Chinese family. We studied a 23-year-old Chinese girl with a history of growth retardation and severe constipation from the age of 3 months, who was diagnosed as having congenital hypothyroidism. Genomic DNA was extracted from peripheral blood samples obtained from the patient's family members. The genomic DNA was sequenced to detect mutations in a panel of genes associated with congenital hypothyroidism. Bioinformatic analysis and structural modelling predicted the potential disease-causing potential mutant genes and the microstructure of the mutant protein, respectively. Western blotting and ELISA were used to measure protein expression, and guaiacol oxidation assay measured the TPO activity of the mutant protein. We identified a compound heterozygous mutation (c.C1993T, c.T2473C) in the TPO gene. Bioinformatic analysis predicted that the TPO mutations were potentially disease causing. Structural modelling predicted damage to the microstructure of the mutant TPO protein. Western blotting and ELISA showed reduced protein levels of the mutant TPO protein compared with that of the wild-type protein. The mutant TPO protein showed weaker activity compared with that of the wild-type protein. A novel compound heterozygous mutation of TPO gene was identified in a Chinese family. This mutation might alter the extracellular microstructure of TPO, and decrease its expression and the activity, resulting in congenital hypothyroidism.
Substances chimiques
Autoantigens
0
Iron-Binding Proteins
0
TPO protein, human
EC 1.11.1.7
Iodide Peroxidase
EC 1.11.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-507Informations de copyright
© 2020 John Wiley & Sons Ltd.
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