Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR)
Yeste Fernández, Diego (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Baz-Redón, Noelia (Vall d'Hebron Institut de Recerca (VHIR))
Antolín, María (Hospital Universitari Vall d'Hebron)
García Arumí, Elena (Hospital Universitari Vall d'Hebron)
Mogas Viñals, Eduard (Vall d'Hebron Institut de Recerca (VHIR))
Campos-Martorell, Ariadna (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
González-Llorens, Núria (Vall d'Hebron Institut de Recerca (VHIR))
Aguilar-Riera, Cristina (Vall d'Hebron Institut de Recerca (VHIR))
Soler Colomer, Laura (Vall d'Hebron Institut de Recerca (VHIR))
Clemente, Maria (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Fernández Cancio, Mónica (Vall d'Hebron Institut de Recerca (VHIR))
Camats Tarruella, Núria (Vall d'Hebron Institut de Recerca (VHIR))

Data:	2024
Resum:	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-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 Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished.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's genotype for a correct diagnostic confirmation.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Thyroid gland ; Congenital hypothyroidism ; Thyroid dyshormonogenesis ; TSHR ; TSH receptor ; Genetic variants ; Functional studies
Publicat a:	International journal of molecular sciences, Vol. 25 Núm. 18 (September 2024) , ISSN 1422-0067

DOI: 10.3390/ijms251810032
PMID: 39337518

14 p, 2.6 MB

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