Your browser doesn't support javascript.
loading
Mutational screening of the TPO and DUOX2 genes in Argentinian children with congenital hypothyroidism due to thyroid dyshormonogenesis.
Molina, Maricel F; Papendieck, Patricia; Sobrero, Gabriela; Balbi, Viviana A; Belforte, Fiorella S; Martínez, Elena Bueno; Adrover, Ezequiela; Olcese, María C; Chiesa, Ana; Miras, Mirta B; González, Verónica G; Pio, Mauricio Gomes; González-Sarmiento, Rogelio; Targovnik, Héctor M; Rivolta, Carina M.
Afiliação
  • Molina MF; Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética/Cátedra de Genética, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Papendieck P; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Sobrero G; Centro de Investigaciones Endocrinológicas, CEDIE-CONICET, División Endocrinología, Hospital de Niños "Ricardo Gutiérrez", Buenos Aires, Argentina.
  • Balbi VA; Servicio de Endocrinología, Hospital de Niños Santísima Trinidad, Córdoba, Argentina.
  • Belforte FS; Servicio de Endocrinología, Hospital de Niños "Sor María Ludovica", La Plata, Argentina.
  • Martínez EB; Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética/Cátedra de Genética, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Adrover E; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Olcese MC; Unidad de Medicina Molecular-Departamento de Medicina, IBMCC and IBSAL, Universidad de Salamanca-CSIC, Salamanca, España.
  • Chiesa A; Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética/Cátedra de Genética, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Miras MB; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
  • González VG; Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética/Cátedra de Genética, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Pio MG; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
  • González-Sarmiento R; Centro de Investigaciones Endocrinológicas, CEDIE-CONICET, División Endocrinología, Hospital de Niños "Ricardo Gutiérrez", Buenos Aires, Argentina.
  • Targovnik HM; Servicio de Endocrinología, Hospital de Niños Santísima Trinidad, Córdoba, Argentina.
  • Rivolta CM; Servicio de Endocrinología, Hospital de Niños "Sor María Ludovica", La Plata, Argentina.
Endocrine ; 77(1): 86-101, 2022 06.
Article em En | MEDLINE | ID: mdl-35507000
PURPOSE: Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the preventable causes of both cognitive and motor deficits. We present a genetic and bioinformatics investigation of rational clinical design in 17 Argentine patients suspected of CH due to thyroid dyshormonogenesis (TDH). METHODS: Next-Generation Sequencing approach was used to identify variants in Thyroid Peroxidase (TPO) and Dual Oxidase 2 (DUOX2) genes. A custom panel targeting 7 genes associated with TDH [(TPO), Iodothyrosine Deiodinase I (IYD), Solute Carrier Family 26 Member 4 (SLC26A4), Thyroglobulin (TG), DUOX2, Dual Oxidase Maturation Factor 2 (DUOXA2), Solute Carrier Family 5 Member 5 (SLC5A5)] and 4 associated with thyroid dysembryogenesis [PAX8, FOXE1, NKX2-1, Thyroid Stimulating Hormone Receptor (TSHR)] has been designed. Additionally, bioinformatic analysis and structural modeling were carried out to predict the disease-causing potential variants. RESULTS: Four novel variants have been identified, two in TPO: c.2749-2 A > C and c.2752_2753delAG, [p.Ser918Cysfs*62] and two variants in DUOX2 gene: c.425 C > G [p.Pro142Arg] and c.2695delC [p.Gln899Serfs*21]. Eighteen identified TPO, DUOX2 and IYD variants were previously described. We identified potentially pahogenic biallelic variants in TPO and DUOX2 in 7 and 2 patients, respectively. We also detected a potentially pathogenic monoallelic variant in TPO and DUOX2 in 7 and 1 patients respectively. CONCLUSIONS: 22 variants have been identified associated with TDH. All described novel mutations occur in domains important for protein structure and function, predicting the TDH phenotype.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoantígenos / Hipotireoidismo Congênito / Proteínas de Ligação ao Ferro / Oxidases Duais / Iodeto Peroxidase Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Child / Humans País/Região como assunto: America do sul / Argentina Idioma: En Revista: Endocrine Assunto da revista: ENDOCRINOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoantígenos / Hipotireoidismo Congênito / Proteínas de Ligação ao Ferro / Oxidases Duais / Iodeto Peroxidase Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Child / Humans País/Região como assunto: America do sul / Argentina Idioma: En Revista: Endocrine Assunto da revista: ENDOCRINOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos