Open AccessThyroid hormone resistance syndrome caused by heterozygous A317T mutation in thyroid hormone receptor β gene
Author(s) -
Qinghua Guo,
Baoan Wang,
Chen-Zhi Wang,
Min Wang,
JenHer Lu,
Zhao-hui Lv,
Yiming Mu
Publication year - 2016
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000004415
Subject(s) - medicine , proband , endocrinology , missense mutation , thyroid , mutation , gene mutation , thyroid hormone receptor beta , thyroid function tests , genetics , hormone receptor , gene , biology , breast cancer , cancer
Background: Thyroid hormone resistance syndrome (THRS) is a rare disorder with increased concentrations of free thyroxine (FT4) and triiodothyronine (FT3), but normal or slightly increased thyroid-stimulating hormone (TSH). The mutations in the thyroid hormone receptor β (THRβ) gene are thought to be the main pathogenesis. Objectives: The aims of this study were to present 1 pedigree of Chinese THRS, summarize their clinical characteristics, and analyze the gene mutation. Methods: The clinical characteristics and thyroid function of the proband and his family members were collected. Gene mutations were analyzed by DNA sequencing. Results: The proband and his mother exhibited symptoms of hyperthyroidism, such as palpitations, heat intolerance, and perspiration. The mother also had atrial fibrillation. The rest of the kindred did not display clinical manifestations of hyper- or hypothyroidism. DNA sequencing revealed a heterozygous G>A missense mutation at position 949 in Exon 9 of THRβ both in the patient and his mother, which led to the transition from alanine to threonine at position 317 of THRβ protein (A317T), whereas the rest of the kindred did not share this mutation. The proband and his mother were diagnosed with pituitary resistance to thyroid hormone. Oral administration of methimazole was stopped and β-receptor blockers were administrated. Conclusions: We present 1 pedigree of THRS with heterozygous A317T mutation in THRβ gene in the proband and his mother, which is the first reported mutation in Chinese and provides a comprehensive review of available literature.