{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:13:46Z","timestamp":1772158426534,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["U-712"],"award-info":[{"award-number":["U-712"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genetic defects in the TSH receptor (TSHR) 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 TSHR variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with TSHR defects and to study in vitro the effect of the genetic variants to establish the genotype\u2013phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4\u2013100 mIU\/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP\u2013response\u2013element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished.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 TSHR 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\u2019s genotype for a correct diagnostic confirmation.<\/jats:p>","DOI":"10.3390\/ijms251810032","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T09:43:13Z","timestamp":1726652593000},"page":"10032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR)"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-6525","authenticated-orcid":false,"given":"Diego","family":"Yeste","sequence":"first","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"},{"name":"CIBERER, ISCIII, 28029 Madrid, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-3413","authenticated-orcid":false,"given":"Noelia","family":"Baz-Red\u00f3n","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"},{"name":"CIBERER, ISCIII, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Antol\u00edn","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Garcia-Arum\u00ed","sequence":"additional","affiliation":[{"name":"CIBERER, ISCIII, 28029 Madrid, Spain"},{"name":"Department of Clinical and Molecular Genetics, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-5364","authenticated-orcid":false,"given":"Eduard","family":"Mogas","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariadna","family":"Campos-Martorell","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0550-4665","authenticated-orcid":false,"given":"N\u00faria","family":"Gonz\u00e1lez-Llorens","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-3743","authenticated-orcid":false,"given":"Cristina","family":"Aguilar-Riera","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Soler-Colomer","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3721-5043","authenticated-orcid":false,"given":"Mar\u00eda","family":"Clemente","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"},{"name":"CIBERER, ISCIII, 28029 Madrid, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Fern\u00e1ndez-Cancio","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"},{"name":"CIBERER, ISCIII, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-8201","authenticated-orcid":false,"given":"N\u00faria","family":"Camats-Tarruella","sequence":"additional","affiliation":[{"name":"Growth and Development Group, Vall d\u2019Hebron Institut de Recerca (VHIR)\u2014Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Spain"},{"name":"CIBERER, ISCIII, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital hypothyroidism","volume":"5","author":"Rastogi","year":"2010","journal-title":"Orphanet J. 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Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10032\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:58:24Z","timestamp":1760111904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":24,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms251810032"],"URL":"https:\/\/doi.org\/10.3390\/ijms251810032","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,18]]}}}