• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

甲状腺激素生物合成障碍和促甲状腺激素受体缺陷患者的遗传和功能研究（）。

Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor ().

机构信息

Growth and Development Group, Vall d'Hebron Institut de Recerca (VHIR)-Pediatric Endocrinology Section, Hospital Universitari Vall d'Hebron (HUVH), 08035 Barcelona, Spain.

CIBERER, ISCIII, 28029 Madrid, Spain.

出版信息

Int J Mol Sci. 2024 Sep 18;25(18):10032. doi: 10.3390/ijms251810032.

DOI:10.3390/ijms251810032
PMID:39337518
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11432690/
Abstract

Genetic defects in the TSH receptor () can cause poor thyroid differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis). The phenotype spectrum is wide: from severe congenital hypothyroidism to mild hyperthyrotropinemia. Over 250 variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with defects and to study in vitro the effect of the genetic variants to establish the genotype-phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4-100 mIU/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP-response-element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six variants, two unpublished. Each variant showed a different in vitro functional profile that was totally or partially deleterious. Depending on the genotype, some of the variants showed partial deficiency in both genotypes, whereas others presented a different effect. In conclusion, the percentage of patients with thyroid dyshormonogenesis and candidate variants in is 3.13%. Our in vitro studies contributed to the confirmation of the pathogenicity of the variants and highlighted the importance of studying the effect of the patient's genotype for a correct diagnostic confirmation.

摘要

TSH 受体（）的遗传缺陷可导致甲状腺分化不良（甲状腺发育不良）和/或甲状腺功能障碍（甲状腺激素生成障碍）。表型谱很广：从严重的先天性甲状腺功能减退症到轻度促甲状腺素升高。已经发表了超过 250 种变异体，但许多在体外都没有特征。我们旨在通过研究 缺陷导致的甲状腺激素生成障碍患者的遗传特征，并研究体外遗传变异的影响，以建立基因型-表型关系。通过高通量基因面板分析了患有甲状腺激素生成障碍的儿科患者（160 例患者，加泰罗尼亚新生儿筛查计划，确认 TSH 范围：18.4-100mIU/L）。进行了测量 TSH 依赖性 cAMP 反应元件激活的体外研究。五位患有轻度或重度甲状腺激素生成障碍的患者表现出六种 变异，其中两种是未发表的。每种变异体显示出不同的体外功能谱，完全或部分具有致病变异。根据基因型，一些变异体在两种基因型中均表现出部分缺乏，而其他变异体则表现出不同的影响。总之，甲状腺激素生成障碍患者和候选变异体在 中的比例为 3.13%。我们的体外研究有助于确认变异体的致病性，并强调了研究患者基因型对正确诊断确认的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/fa3b4c885e9e/ijms-25-10032-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/7e87b7bee49f/ijms-25-10032-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/8195f918d1f8/ijms-25-10032-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/61cedb9d1e76/ijms-25-10032-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/fa3b4c885e9e/ijms-25-10032-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/7e87b7bee49f/ijms-25-10032-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/8195f918d1f8/ijms-25-10032-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/61cedb9d1e76/ijms-25-10032-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10fc/11432690/fa3b4c885e9e/ijms-25-10032-g004.jpg

相似文献

1
Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor ().甲状腺激素生物合成障碍和促甲状腺激素受体缺陷患者的遗传和功能研究（）。
Int J Mol Sci. 2024 Sep 18;25(18):10032. doi: 10.3390/ijms251810032.
2
[Pathogenic variants in children with thyroid dysgenesis].[甲状腺发育不全儿童的致病变异]
Probl Endokrinol (Mosk). 2023 Feb 25;69(1):76-85. doi: 10.14341/probl13210.
3
Genetics of Gland- or Hypoplastic Congenital Hypothyroidism in Macedonia.马其顿的腺体或发育不全性先天性甲状腺功能减退症的遗传学。
Front Endocrinol (Lausanne). 2020 Jul 14;11:413. doi: 10.3389/fendo.2020.00413. eCollection 2020.
4
Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion.先天性甲状腺功能减退症患者中促甲状腺激素受体铰链区新型序列变异p.S304R的功能特性及与该基因部分其他已知突变的类比
J Pediatr Endocrinol Metab. 2015 Jul;28(7-8):777-84. doi: 10.1515/jpem-2014-0194.
5
Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis.对100例先天性甲状腺功能减退症和无甲状腺症的中国患者进行NKX2.1、FOXE1、PAX8、NKX2.5和TSHR的下一代测序。
Clin Chim Acta. 2017 Jul;470:36-41. doi: 10.1016/j.cca.2017.04.020. Epub 2017 Apr 25.
6
Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis.沙特阿拉伯先天性甲状腺功能减退症的分子分析：SLC26A7 突变是甲状腺激素生成障碍的新缺陷。
J Clin Endocrinol Metab. 2018 May 1;103(5):1889-1898. doi: 10.1210/jc.2017-02202.
7
Long-term outcome of loss-of-function mutations in thyrotropin receptor gene.促甲状腺激素受体基因功能丧失性突变的长期结果
Thyroid. 2015 Mar;25(3):292-9. doi: 10.1089/thy.2014.0311. Epub 2015 Jan 28.
8
Identification of southern Taiwan genetic variants in thyroid dyshormonogenesis through whole-exome sequencing.通过全外显子组测序鉴定台湾南部甲状腺激素合成障碍的遗传变异
Kaohsiung J Med Sci. 2024 Aug;40(8):744-756. doi: 10.1002/kjm2.12871. Epub 2024 Jun 25.
9
Functional studies of new TSH receptor (TSHr) mutations identified in patients affected by hypothyroidism or isolated hyperthyrotrophinaemia.对甲状腺功能减退症或孤立性促甲状腺激素血症患者中鉴定出的新型促甲状腺激素受体（TSHr）突变的功能研究。
Clin Endocrinol (Oxf). 2009 Feb;70(2):335-8. doi: 10.1111/j.1365-2265.2008.03333.x. Epub 2008 Aug 22.
10
Genetic Evaluation of Congenital Hypothyroidism with Gland Using Targeted Exome Sequencing.使用靶向外显子组测序对先天性甲状腺功能减退症的腺体进行遗传评估。
Ann Clin Lab Sci. 2021 Jan;51(1):73-81.

引用本文的文献

1
Investigating gene variants in consanguineous families: novel insights into variable expression in familial congenital hypothyroidism.对近亲家庭中的基因变异进行研究：家族性先天性甲状腺功能减退症可变表达的新见解。
Front Endocrinol (Lausanne). 2025 May 5;16:1559281. doi: 10.3389/fendo.2025.1559281. eCollection 2025.

本文引用的文献

1
Search and sequence analysis tools services from EMBL-EBI in 2022.2022 年 EMBL-EBI 的搜索和序列分析工具服务。
Nucleic Acids Res. 2022 Jul 5;50(W1):W276-W279. doi: 10.1093/nar/gkac240.
2
Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology.先天性甲状腺功能减退症：2020-2021 年共识指南更新——一项由 ENDO-欧洲参考网络倡议发起并得到欧洲儿科内分泌学会和欧洲内分泌学会认可的倡议。
Thyroid. 2021 Mar;31(3):387-419. doi: 10.1089/thy.2020.0333.
3
Inferring the molecular and phenotypic impact of amino acid variants with MutPred2.
使用 MutPred2 推断氨基酸变异的分子和表型影响。
Nat Commun. 2020 Nov 20;11(1):5918. doi: 10.1038/s41467-020-19669-x.
4
Phenotypic Variability of Patients With PAX8 Variants Presenting With Congenital Hypothyroidism and Eutopic Thyroid.PAX8 变异患者伴发先天性甲状腺功能减退和甲状腺组织正常时的表型变异性。
J Clin Endocrinol Metab. 2021 Jan 1;106(1):e152-e170. doi: 10.1210/clinem/dgaa711.
5
The Molecular Function and Clinical Role of Thyroid Stimulating Hormone Receptor in Cancer Cells.甲状腺刺激素受体在癌细胞中的分子功能和临床作用。
Cells. 2020 Jul 20;9(7):1730. doi: 10.3390/cells9071730.
6
Insights into the Basal Activity and Activation Mechanism of the β1 Adrenergic Receptor Using Native Mass Spectrometry.使用天然质谱法深入了解β1 肾上腺素能受体的基础活性和激活机制。
J Am Soc Mass Spectrom. 2019 Mar;30(3):529-537. doi: 10.1007/s13361-018-2110-z. Epub 2018 Dec 3.
7
Identification of compound heterozygous mutations (R109Q and R450H) in a patient with nonclassic TSH resistance and functional characterization of the mutant receptors.一名非典型促甲状腺激素抵抗患者中复合杂合突变（R109Q和R450H）的鉴定及突变受体的功能特性分析
Clin Pediatr Endocrinol. 2018;27(3):123-130. doi: 10.1297/cpe.27.123. Epub 2018 Jul 31.
8
Genetics of Primary Congenital Hypothyroidism.原发性先天性甲状腺功能减退症的遗传学
Pediatr Endocrinol Rev. 2018 Mar;15(3):200-215. doi: 10.17458/per.vol15.2018.zst.geneticsprimaryhypothyroidism.
9
Resistance to thyrotropin.促甲状腺素抵抗
Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):183-194. doi: 10.1016/j.beem.2017.03.004. Epub 2017 Mar 30.
10
HGVS Recommendations for the Description of Sequence Variants: 2016 Update.《人类基因组变异协会（HGVS）序列变异描述建议：2016年更新》
Hum Mutat. 2016 Jun;37(6):564-9. doi: 10.1002/humu.22981. Epub 2016 Mar 25.