Patients with Thyroid Dyshormonogenesis and DUOX2 Variants

Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to p...

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Detalles Bibliográficos
Autores: Baz-Redón, Noelia|||0000-0003-1704-3413, Antolín, María|||0000-0001-5623-6862, Clemente, Maria|||0000-0002-3721-5043, Campos-Martorell, Ariadna|||0000-0002-8134-4934, Mogas Viñals, Eduard|||0000-0001-8501-5364, Fernández Cancio, Mónica|||0000-0003-1872-3488, Zafon, Elisenda, García Arumí, Elena|||0000-0003-1848-005X, Soler, Laura, González-Llorens, Núria|||0000-0003-0550-4665, Aguilar-Riera, Cristina|||0000-0001-5256-3743, Camats Tarruella, Núria|||0000-0002-4863-8201, Yeste Fernández, Diego|||0000-0002-6620-6525
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:319977
Acceso en línea:https://ddd.uab.cat/record/319977
https://dx.doi.org/urn:doi:10.3390/ijms25158473
Access Level:acceso abierto
Palabra clave:Congenital hypothyroidism
CH
Thyroid dyshormonogenesis
Dual oxidase 2
DUOX2
Phenotypic variability
Descripción
Sumario:Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype-phenotype correlation in patients with THD and candidate variants in DUOX2. A total of 31 (19.38%) patients from the Catalan Neonatal Screening Program presented with variants in DUOX2 that could explain their phenotype. Fifteen (48.39%) patients were compound heterozygous, 10 (32.26%) heterozygous, and 4 (12.90%) homozygous. In addition, 8 (26.67%) of these patients presented variants in other genes. A total of 35 variants were described, 10 (28.57%) of these variants have not been previously reported in literature. The most frequent variant in our cohort was c.2895_2898del/p.(Phe966SerfsTer29), classified as pathogenic according to reported functional studies. The final diagnosis of this cohort was permanent THD in 21 patients and transient THD in 10, according to reevaluation and/or need for treatment with levothyroxine. A clear genotype-phenotype correlation could not be identified; therefore, functional studies are necessary to confirm the pathogenicity of the variants.