Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19

Autores
Targovnik, Hector Manuel; Edouard, Thomas; Varela, Viviana; Tauber, Maithé; Citterio, Cintia Eliana; González Sarmiento, Rogelio; Rivolta, Carina Marcela
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid gland. To date, 52 mutations of the TG gene have been identified in humans. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report a French patient with congenital hypothyroidism, mild enlarged thyroid gland and low levels of serum TG. Sequencing of DNA, genotyping, expression of chimeric minigenes as well as bioinformatics analysis were performed. DNA sequencing identified the presence of compound heterozygous mutations in the TG gene: the paternal mutation consists of a c.3788?3789insT or c.3788dupT, whereas the maternal mutation consists of g.IVS19+3_+4delAT. Minigene analysis of the g.IVS19+3_+4delAT mutant showed that the exon 19 is skipped during pre-mRNA splicing or partially included by use of cryptic 50 splice site located to 100 nucleotides downstream of the wild type exon intron junction. The c.3788?3789insT mutation results in a putative truncated protein of 1245 amino acids, whereas g.IVS19+3_4delAT mutation originates two putative truncated proteins of 1330 and 1349 amino acids. In conclusion, we show that the g.IVS19+3_+4delAT mutation promotes the activation of a cryptic donor splice site in the exon 19 of the TG gene. These results open up new perspectives in the knowledge of the mechanism of splicing for the TG pre-mRNA.
Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: Edouard, Thomas. Instituto Polytechnique de Toulouse; Francia
Fil: Varela, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: Tauber, Maithé. Instituto Polytechnique de Toulouse; Francia
Fil: Citterio, Cintia Eliana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: González Sarmiento, Rogelio. Universidad de Salamanca; España
Fil: Rivolta, Carina Marcela. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Materia
CONGENITAL GOITER
THYROGLOBULIN GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATION
CRIPTIC SPLICE SITE
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:11336/268699
Acceder
id CONICETDig_f811e3986eee2b139f12262af754fa84
oai_identifier_str oai:ri.conicet.gov.ar:11336/268699
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19Targovnik, Hector ManuelEdouard, ThomasVarela, VivianaTauber, MaithéCitterio, Cintia ElianaGonzález Sarmiento, RogelioRivolta, Carina MarcelaCONGENITAL GOITERTHYROGLOBULIN GENEMUTATIONCOMPOUND HETEROZYGOUS MUTATIONCRIPTIC SPLICE SITEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid gland. To date, 52 mutations of the TG gene have been identified in humans. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report a French patient with congenital hypothyroidism, mild enlarged thyroid gland and low levels of serum TG. Sequencing of DNA, genotyping, expression of chimeric minigenes as well as bioinformatics analysis were performed. DNA sequencing identified the presence of compound heterozygous mutations in the TG gene: the paternal mutation consists of a c.3788?3789insT or c.3788dupT, whereas the maternal mutation consists of g.IVS19+3_+4delAT. Minigene analysis of the g.IVS19+3_+4delAT mutant showed that the exon 19 is skipped during pre-mRNA splicing or partially included by use of cryptic 50 splice site located to 100 nucleotides downstream of the wild type exon intron junction. The c.3788?3789insT mutation results in a putative truncated protein of 1245 amino acids, whereas g.IVS19+3_4delAT mutation originates two putative truncated proteins of 1330 and 1349 amino acids. In conclusion, we show that the g.IVS19+3_+4delAT mutation promotes the activation of a cryptic donor splice site in the exon 19 of the TG gene. These results open up new perspectives in the knowledge of the mechanism of splicing for the TG pre-mRNA.Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: Edouard, Thomas. Instituto Polytechnique de Toulouse; FranciaFil: Varela, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: Tauber, Maithé. Instituto Polytechnique de Toulouse; FranciaFil: Citterio, Cintia Eliana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: González Sarmiento, Rogelio. Universidad de Salamanca; EspañaFil: Rivolta, Carina Marcela. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaElsevier Ireland2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/268699Targovnik, Hector Manuel; Edouard, Thomas; Varela, Viviana; Tauber, Maithé; Citterio, Cintia Eliana; et al.; Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19; Elsevier Ireland; Molecular and Cellular Endocrinology; 348; 1; 1-2012; 313-3210303-7207CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720711005582info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2011.09.024info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:44:16Zoai:ri.conicet.gov.ar:11336/268699instacron: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:34982025-10-15 14:44:16.959CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
title Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
spellingShingle Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
Targovnik, Hector Manuel
CONGENITAL GOITER
THYROGLOBULIN GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATION
CRIPTIC SPLICE SITE
title_short Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
title_full Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
title_fullStr Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
title_full_unstemmed Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
title_sort Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19
dc.creator.none.fl_str_mv Targovnik, Hector Manuel
Edouard, Thomas
Varela, Viviana
Tauber, Maithé
Citterio, Cintia Eliana
González Sarmiento, Rogelio
Rivolta, Carina Marcela
author Targovnik, Hector Manuel
author_facet Targovnik, Hector Manuel
Edouard, Thomas
Varela, Viviana
Tauber, Maithé
Citterio, Cintia Eliana
González Sarmiento, Rogelio
Rivolta, Carina Marcela
author_role author
author2 Edouard, Thomas
Varela, Viviana
Tauber, Maithé
Citterio, Cintia Eliana
González Sarmiento, Rogelio
Rivolta, Carina Marcela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CONGENITAL GOITER
THYROGLOBULIN GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATION
CRIPTIC SPLICE SITE
topic CONGENITAL GOITER
THYROGLOBULIN GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATION
CRIPTIC SPLICE SITE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid gland. To date, 52 mutations of the TG gene have been identified in humans. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report a French patient with congenital hypothyroidism, mild enlarged thyroid gland and low levels of serum TG. Sequencing of DNA, genotyping, expression of chimeric minigenes as well as bioinformatics analysis were performed. DNA sequencing identified the presence of compound heterozygous mutations in the TG gene: the paternal mutation consists of a c.3788?3789insT or c.3788dupT, whereas the maternal mutation consists of g.IVS19+3_+4delAT. Minigene analysis of the g.IVS19+3_+4delAT mutant showed that the exon 19 is skipped during pre-mRNA splicing or partially included by use of cryptic 50 splice site located to 100 nucleotides downstream of the wild type exon intron junction. The c.3788?3789insT mutation results in a putative truncated protein of 1245 amino acids, whereas g.IVS19+3_4delAT mutation originates two putative truncated proteins of 1330 and 1349 amino acids. In conclusion, we show that the g.IVS19+3_+4delAT mutation promotes the activation of a cryptic donor splice site in the exon 19 of the TG gene. These results open up new perspectives in the knowledge of the mechanism of splicing for the TG pre-mRNA.
Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: Edouard, Thomas. Instituto Polytechnique de Toulouse; Francia
Fil: Varela, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: Tauber, Maithé. Instituto Polytechnique de Toulouse; Francia
Fil: Citterio, Cintia Eliana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología 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: González Sarmiento, Rogelio. Universidad de Salamanca; España
Fil: Rivolta, Carina Marcela. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
description Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid gland. To date, 52 mutations of the TG gene have been identified in humans. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report a French patient with congenital hypothyroidism, mild enlarged thyroid gland and low levels of serum TG. Sequencing of DNA, genotyping, expression of chimeric minigenes as well as bioinformatics analysis were performed. DNA sequencing identified the presence of compound heterozygous mutations in the TG gene: the paternal mutation consists of a c.3788?3789insT or c.3788dupT, whereas the maternal mutation consists of g.IVS19+3_+4delAT. Minigene analysis of the g.IVS19+3_+4delAT mutant showed that the exon 19 is skipped during pre-mRNA splicing or partially included by use of cryptic 50 splice site located to 100 nucleotides downstream of the wild type exon intron junction. The c.3788?3789insT mutation results in a putative truncated protein of 1245 amino acids, whereas g.IVS19+3_4delAT mutation originates two putative truncated proteins of 1330 and 1349 amino acids. In conclusion, we show that the g.IVS19+3_+4delAT mutation promotes the activation of a cryptic donor splice site in the exon 19 of the TG gene. These results open up new perspectives in the knowledge of the mechanism of splicing for the TG pre-mRNA.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/268699
Targovnik, Hector Manuel; Edouard, Thomas; Varela, Viviana; Tauber, Maithé; Citterio, Cintia Eliana; et al.; Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19; Elsevier Ireland; Molecular and Cellular Endocrinology; 348; 1; 1-2012; 313-321
0303-7207
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268699
identifier_str_mv Targovnik, Hector Manuel; Edouard, Thomas; Varela, Viviana; Tauber, Maithé; Citterio, Cintia Eliana; et al.; Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19; Elsevier Ireland; Molecular and Cellular Endocrinology; 348; 1; 1-2012; 313-321
0303-7207
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720711005582
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2011.09.024
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.22299

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