Dataset Information

Thyroid hormone resistance syndrome caused by heterozygous A317T mutation in thyroid hormone receptor ? gene: Report of one Chinese pedigree and review of the literature.

ABSTRACT: 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 ? (THR?) gene are thought to be the main pathogenesis.The aims of this study were to present 1 pedigree of Chinese THRS, summarize their clinical characteristics, and analyze the gene mutation.The clinical characteristics and thyroid function of the proband and his family members were collected. Gene mutations were analyzed by DNA sequencing.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 THR? both in the patient and his mother, which led to the transition from alanine to threonine at position 317 of THR? 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 ?-receptor blockers were administrated.We present 1 pedigree of THRS with heterozygous A317T mutation in THR? gene in the proband and his mother, which is the first reported mutation in Chinese and provides a comprehensive review of available literature.

SUBMITTER: Guo QH

PROVIDER: S-EPMC5370793 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Thyroid hormone resistance syndrome caused by heterozygous A317T mutation in thyroid hormone receptor β gene: Report of one Chinese pedigree and review of the literature.

Guo Qing-Hua QH Wang Bao-An BA Wang Chen-Zhi CZ Wang Min M Lu Ju-Ming JM Lv Zhao-Hui ZH Mu Yi-Ming YM

Medicine 20160801 33

<h4>Background</h4>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.<h4>Objectives</h4>The aims of this study were to present 1 pedigree of Chinese THRS, summarize their clinical characteristics, and analyze the gene mutation.<h4>Methods ...[more]

PMID: 27537566

Similar Datasets

Project description:Objective: To explore the molecular pathogenesis of a family with hereditary factor Ⅴ (FⅤ) deficiency. Methods: All the exons, flanking sequences, 5' and 3' untranslated regions of the F5 of the proband, and the corresponding mutation sites of the family members were analyzed via direct DNA sequencing. The CAT measurement was used to detect the amount of thrombin produced. The ClustalX software was used to analyze the conservation of mutation sites. The online bioinformatics software, Mutation Taster, PolyPhen-2, PROVEAN, LRT, and SIFT were applied to predict the effects of mutation sites on protein function. The Swiss-PdbViewer software was used to analyze the changes in the protein model and intermolecular force before and after amino acid variation. Results: The proband had a heterozygous missense mutation c.1258G>T (p.Gly392Cys) in exon 8 of the F5, and a heterozygous deletion mutation c.4797delG (p.Glu1572Lys fsX19) in exon 14, which results in a frameshift and produces a truncated protein. Her grandfather and father had p.Gly392Cys heterozygous variation, whereas her maternal grandmother, mother, little aunt, and cousin all had p.Glu1572LysfsX19 heterozygous variation. The ratio of proband's thrombin generation delay to peak time was significantly increased. Conservation analysis results showed that p.Gly392 was located in a conserved region among the 10 homologous species. Five online bioinformatics software predicted that p.Gly392Cys was pathogenic, and Mutation Taster also predicted p.Glu1572Lys fsX19 as a pathogenic variant. Protein model analysis showed that the replacement of Gly392 by Cys392 can lead to the extension of the original hydrogen bond and the formation of a new steric hindrance, which affected the stability of the protein structure. Conclusion: The c.1258G>T heterozygous missense mutation in exon 8 and the c.4797delG heterozygous deletion mutation in exon 14 of the F5 may be responsible for the decrease of FⅤ levels in this family.

Project description:BackgroundTo summarize the clinical characteristics, genetics and follow-up data of four children with thyroid hormone resistance (RTH) syndrome and review the related literatures.MethodsThe clinical data of the four children diagnosed with RTH syndrome in our hospital from 2018 to 2020 were retrospectively analyzed. Next-generation sequencing of the candidate genes related to thyroid diseases was performed using the blood collected from all the children and their parents who signed an informed consent. Then, relevant cases were retrieved on medical literature databases for analysis and summary.ResultsAmong the four cases, three cases of goiter; two cases of tachycardia, palpitations, personality change, hyperactivity, weight loss; one case of academic performance decline, and no hearing and vision loss were observed. Laboratory thyroid function tests indicated a mild increase in free triiodothyronine and with or without increased free thyroxine levels. Thyroid-stimulating hormone (TSH) levels were normal or slightly elevated, but thyrotropin receptor autoantibodies were negative. Octreotide inhibition test showed that the TSH levels of all the children decreased by more than 50% compared with the basal value (the genes of four cases were positive). However, magnetic resonance imaging of the pituitary gland showed no abnormalities. Related gene detection in the children and their families showed that four cases had THRB mutations: two proband mutations were from their fathers, and two cases had de novo mutations.ConclusionsThe clinical manifestations of pediatric RTH syndrome vary, and the diagnosis mainly depends on thyroid function tests. Heterozygous mutations in THRB are overall rare, even if with the advanced development of next-generation sequencing, not all the children with RTH syndrome have mutations. Furthermore, octreotide inhibition tests cannot be used as a diagnostic criterion to distinguish RTH syndrome from pituitary tumors in children.

Project description:BackgroundRubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant inheritable disorder caused by CREBBP and EP300 mutations, while atypical RSTS harbouring variant from the same genes but not obvious resembling RSTS. There are only a few cases of Menke-Hennekam syndrome (MKHK) with variant of exon 30 or 31 of CREBBP or EP300 gene have been reported that not resembling RSTS recent years. Atypical RSTS cannot be accurately classified as MKHK, nor is it easy to identify the obvious classic characteristics of RSTS. The clinical manifestations and genetic variation of atypical RSTS are not fully understood.Case presentationWe present a Chinese core family with a girl had recurrent respiratory tract infection and developmental delay. The patient with language and motor mild development retardation, she has slight abnormal facial features, mild hirsutism and post-axial hexadactylia of left foot. Her cisterna magna is enlarged to connect with the fourth ventricle, and the ventricular system is enlarged. She has a malacia beside the posterior horn of the left lateral ventricle. The patient has primary low immunoglobulin G and A, but her level of immunoglobulin M content in blood is normal. The patient harbors a novel heterozygous frameshift variant of c.2499dupG in exon 14 of EP300 gene, that it is proved to de novo origin. The mutation is judged to be a pathogenic mutation, and it has high-grade pathogenic evidence.ConclusionThe clinical and genetic evaluation of this case corroborates that clinical features caused by c.2499dupG in exon 14 of EP300 are less marked than RSTS2 patient although it is difficult to establish an accurate genotype-phenotype correlation. Our additional case also helps to deepen the clinical and genetic spectrum in this disorder. The case provides a novel mutation of EP300 and enriches the phenotypes related with the gene. We have contributed new variation and disease information for guardians and doctors to broaden the knowledge about EP300-RSTS genotype and phenotype, this may contribute to ameliorate the health management of patients and improve the genetic counseling to the families.

Dataset Information

Thyroid hormone resistance syndrome caused by heterozygous A317T mutation in thyroid hormone receptor ? gene: Report of one Chinese pedigree and review of the literature.

Publications

Thyroid hormone resistance syndrome caused by heterozygous A317T mutation in thyroid hormone receptor β gene: Report of one Chinese pedigree and review of the literature.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets