Related Experiment Video
Updated: Dec 3, 2025
Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Thyroid hormone resistance syndrome with P453T mutation in thyroid hormone receptor β gene: A pedigree report
Ayiguli Yusufu1, Wen-Jing Chen2, Ming-Chen Zhang1
1Department of Endocrinology, Xinjiang Medical University affiliated First Hospital.
Rationale:
Thyroid hormone resistance syndrome (THRS) is an inherited condition characterized by reduced responsiveness of target tissues to thyroid hormone. Due to their nonspecific symptomatic manifestations, these patients can be misdiagnosed. This study reports a pedigree with THRS caused by a mutation in the thyroid hormone receptor β (THRβ) gene.
Patient Concern:
The proband, a 36-year-old woman at 19+4 weeks of gestation, was referred to our hospital because of abnormal thyroid function results. She was diagnosed with hyperthyroidism in October 2015, and had been treated with methimazole until her pregnancy.
Diagnosis:
The proband and 2 of her children were diagnosed with THRS based on genetic analysis. Sequence analysis of the THRβ gene showed a heterozygous mutation C>A located at exon 10. The mutation results in a change in proline for threonine at amino acid position 453, P453T.
Interventions:
No treatment will fully and specifically correct the defect. All 3 patients were in normal metabolic status, and thus treatment was not required.
Outcomes:
During a 2-year follow-up period, none of them had any complaints. The 20-year-old son (167 cm in height) and the 18-year-old daughter (150 cm in height) both had low academic performance.
Lessons:
Elevated serum thyroid hormone (TH) levels associated with nonsuppressed thyroid-stimulating hormone (TSH) levels usually leads to the diagnosis of THRS. Genetic analysis provides a short cut to diagnosis and the treatment should be based on the patient's clinical manifestations.
Insights
Thyroid hormone resistance syndrome (THRS) is an inherited disorder. Genetic analysis of the thyroid hormone receptor beta (THRβ) gene identified a mutation causing THRS in a three-generation family.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Thyroid hormone resistance syndrome (THRS) is an inherited disorder with variable symptoms, often leading to misdiagnosis.
- Reduced tissue responsiveness to thyroid hormone characterizes THRS.
- This study investigates a family with THRS linked to a thyroid hormone receptor beta (THRβ) gene mutation.
Purpose of the Study:
- To identify the genetic cause of THRS in a familial pedigree.
- To characterize the clinical presentation and genetic mutation associated with THRS.
Main Methods:
- Pedigree analysis and clinical evaluation of affected individuals.
- Sequence analysis of the thyroid hormone receptor beta (THRβ) gene.
- Genetic testing to confirm THRS diagnosis.
Main Results:
- A heterozygous mutation (C>A, P453T) in the THRβ gene was identified in the proband and two children.
- All affected individuals presented with normal metabolic status, requiring no specific treatment.
- Two affected children exhibited low academic performance during the follow-up period.
Conclusions:
- Genetic analysis of the THRβ gene is crucial for accurate THRS diagnosis.
- Elevated thyroid hormone with non-suppressed TSH levels suggests THRS.
- Treatment decisions for THRS should be guided by individual clinical manifestations.
Related Concept Videos
01:35Pedigree Analysis
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:43Incomplete Dominance