Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene

Autores
Belforte, Fiorella Sabrina; Miras, Mirta Beatriz; Olcese, María Cecilia; Sobrero, Gabriela Maria; Testa, Graciela; Franchioni de Muñoz, Noemi Liliana; Gruñeiro Papendieck, Laura; Chiesa, Ana Elena; González Sarmiento, Rogelio; Targovnik, Hector Manuel; Rivolta, Carina Marcela
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25. It comprises 17 exons, covers approximately 150 kb of genomic DNA and codes 933 amino acids. Objetives: In this study, we characterize the clinical and molecular basis of seven patients from four unrelated families with congenital hypothyroidism (CH) because of IOD. Design and Methods: All patients underwent clinical, biochemical and imaging evaluation. The promoter and the complete coding regions of the human TPO along with the flanking intronic regions were analysed by single-strand conformation polymorphism analysis and direct DNA sequencing. Segregation analysis of mutations was carried out, and the effect of the novel missense identified mutations was investigated by 'in silico' studies. Results: All subjects had congenital and persistent primary hypothyroidism. Three novel mutations: c.796C>T [p.Q266X], c.1784G>A [p.R595K] and c.2000G>A [p.G667D] and a previously reported mutation: c.1186-1187insGGCC [p.R396fsX472] have been identified. Four patients were compound heterozygous for p.R396fsX472/p.R595K mutations, two patients were homozygous for p.R595K, and the remaining patient was a compound heterozygous for p.Q266X/p.G667D. Conclusions: Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.
Fil: Belforte, Fiorella Sabrina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Miras, Mirta Beatriz. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Sobrero, Gabriela Maria. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Testa, Graciela. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Franchioni de Muñoz, Noemi Liliana. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Gruñeiro Papendieck, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: González Sarmiento, Rogelio. Universidad de Salamanca; España
Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Rivolta, Carina Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Materia
CONGENITAL GOITER
HYPOTHYROIDISM
THYROID PEROXIDASE
MUTATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/113293
Acceder
id CONICETDig_04e0c6781d5ca80903968962971b4927
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase geneBelforte, Fiorella SabrinaMiras, Mirta BeatrizOlcese, María CeciliaSobrero, Gabriela MariaTesta, GracielaFranchioni de Muñoz, Noemi LilianaGruñeiro Papendieck, LauraChiesa, Ana ElenaGonzález Sarmiento, RogelioTargovnik, Hector ManuelRivolta, Carina MarcelaCONGENITAL GOITERHYPOTHYROIDISMTHYROID PEROXIDASEMUTATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25. It comprises 17 exons, covers approximately 150 kb of genomic DNA and codes 933 amino acids. Objetives: In this study, we characterize the clinical and molecular basis of seven patients from four unrelated families with congenital hypothyroidism (CH) because of IOD. Design and Methods: All patients underwent clinical, biochemical and imaging evaluation. The promoter and the complete coding regions of the human TPO along with the flanking intronic regions were analysed by single-strand conformation polymorphism analysis and direct DNA sequencing. Segregation analysis of mutations was carried out, and the effect of the novel missense identified mutations was investigated by 'in silico' studies. Results: All subjects had congenital and persistent primary hypothyroidism. Three novel mutations: c.796C>T [p.Q266X], c.1784G>A [p.R595K] and c.2000G>A [p.G667D] and a previously reported mutation: c.1186-1187insGGCC [p.R396fsX472] have been identified. Four patients were compound heterozygous for p.R396fsX472/p.R595K mutations, two patients were homozygous for p.R595K, and the remaining patient was a compound heterozygous for p.Q266X/p.G667D. Conclusions: Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.Fil: Belforte, Fiorella Sabrina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Miras, Mirta Beatriz. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sobrero, Gabriela Maria. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Testa, Graciela. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Franchioni de Muñoz, Noemi Liliana. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Gruñeiro Papendieck, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: González Sarmiento, Rogelio. Universidad de Salamanca; EspañaFil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rivolta, Carina Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaWiley Blackwell Publishing, Inc2012-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/113293Belforte, Fiorella Sabrina; Miras, Mirta Beatriz; Olcese, María Cecilia; Sobrero, Gabriela Maria; Testa, Graciela; et al.; Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene; Wiley Blackwell Publishing, Inc; Clinical Endocrinology; 76; 4; 4-2012; 568-5760300-0664CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2265.2011.04249.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2265.2011.04249.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:16Zoai:ri.conicet.gov.ar:11336/113293instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:53:17.0CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
title Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
spellingShingle Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
Belforte, Fiorella Sabrina
CONGENITAL GOITER
HYPOTHYROIDISM
THYROID PEROXIDASE
MUTATION
title_short Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
title_full Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
title_fullStr Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
title_full_unstemmed Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
title_sort Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
dc.creator.none.fl_str_mv Belforte, Fiorella Sabrina
Miras, Mirta Beatriz
Olcese, María Cecilia
Sobrero, Gabriela Maria
Testa, Graciela
Franchioni de Muñoz, Noemi Liliana
Gruñeiro Papendieck, Laura
Chiesa, Ana Elena
González Sarmiento, Rogelio
Targovnik, Hector Manuel
Rivolta, Carina Marcela
author Belforte, Fiorella Sabrina
author_facet Belforte, Fiorella Sabrina
Miras, Mirta Beatriz
Olcese, María Cecilia
Sobrero, Gabriela Maria
Testa, Graciela
Franchioni de Muñoz, Noemi Liliana
Gruñeiro Papendieck, Laura
Chiesa, Ana Elena
González Sarmiento, Rogelio
Targovnik, Hector Manuel
Rivolta, Carina Marcela
author_role author
author2 Miras, Mirta Beatriz
Olcese, María Cecilia
Sobrero, Gabriela Maria
Testa, Graciela
Franchioni de Muñoz, Noemi Liliana
Gruñeiro Papendieck, Laura
Chiesa, Ana Elena
González Sarmiento, Rogelio
Targovnik, Hector Manuel
Rivolta, Carina Marcela
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CONGENITAL GOITER
HYPOTHYROIDISM
THYROID PEROXIDASE
MUTATION
topic CONGENITAL GOITER
HYPOTHYROIDISM
THYROID PEROXIDASE
MUTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25. It comprises 17 exons, covers approximately 150 kb of genomic DNA and codes 933 amino acids. Objetives: In this study, we characterize the clinical and molecular basis of seven patients from four unrelated families with congenital hypothyroidism (CH) because of IOD. Design and Methods: All patients underwent clinical, biochemical and imaging evaluation. The promoter and the complete coding regions of the human TPO along with the flanking intronic regions were analysed by single-strand conformation polymorphism analysis and direct DNA sequencing. Segregation analysis of mutations was carried out, and the effect of the novel missense identified mutations was investigated by 'in silico' studies. Results: All subjects had congenital and persistent primary hypothyroidism. Three novel mutations: c.796C>T [p.Q266X], c.1784G>A [p.R595K] and c.2000G>A [p.G667D] and a previously reported mutation: c.1186-1187insGGCC [p.R396fsX472] have been identified. Four patients were compound heterozygous for p.R396fsX472/p.R595K mutations, two patients were homozygous for p.R595K, and the remaining patient was a compound heterozygous for p.Q266X/p.G667D. Conclusions: Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.
Fil: Belforte, Fiorella Sabrina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Miras, Mirta Beatriz. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Sobrero, Gabriela Maria. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Testa, Graciela. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Franchioni de Muñoz, Noemi Liliana. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Gruñeiro Papendieck, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: González Sarmiento, Rogelio. Universidad de Salamanca; España
Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Rivolta, Carina Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
description Background: Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25. It comprises 17 exons, covers approximately 150 kb of genomic DNA and codes 933 amino acids. Objetives: In this study, we characterize the clinical and molecular basis of seven patients from four unrelated families with congenital hypothyroidism (CH) because of IOD. Design and Methods: All patients underwent clinical, biochemical and imaging evaluation. The promoter and the complete coding regions of the human TPO along with the flanking intronic regions were analysed by single-strand conformation polymorphism analysis and direct DNA sequencing. Segregation analysis of mutations was carried out, and the effect of the novel missense identified mutations was investigated by 'in silico' studies. Results: All subjects had congenital and persistent primary hypothyroidism. Three novel mutations: c.796C>T [p.Q266X], c.1784G>A [p.R595K] and c.2000G>A [p.G667D] and a previously reported mutation: c.1186-1187insGGCC [p.R396fsX472] have been identified. Four patients were compound heterozygous for p.R396fsX472/p.R595K mutations, two patients were homozygous for p.R595K, and the remaining patient was a compound heterozygous for p.Q266X/p.G667D. Conclusions: Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.
publishDate 2012
dc.date.none.fl_str_mv 2012-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/113293
Belforte, Fiorella Sabrina; Miras, Mirta Beatriz; Olcese, María Cecilia; Sobrero, Gabriela Maria; Testa, Graciela; et al.; Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene; Wiley Blackwell Publishing, Inc; Clinical Endocrinology; 76; 4; 4-2012; 568-576
0300-0664
CONICET Digital
CONICET
url http://hdl.handle.net/11336/113293
identifier_str_mv Belforte, Fiorella Sabrina; Miras, Mirta Beatriz; Olcese, María Cecilia; Sobrero, Gabriela Maria; Testa, Graciela; et al.; Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene; Wiley Blackwell Publishing, Inc; Clinical Endocrinology; 76; 4; 4-2012; 568-576
0300-0664
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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