Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review

Autores
Belforte, Fiorella Sabrina; Olcese, María Cecilia; Siffo, Sofía; Papendieck, Patricia; Enacan, Rosa E.; Gruñeiro-Papendieck, Laura; Chiesa, Ana Elena; Targovnik, Hector Manuel; Rivolta, Carina Marcela
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: DUOX2 deficiency is a transient or permanent disorder that results in thyroid dyshormonogenesis. The purpose of this study was to identify and characterize new mutations in the DUOX2 gene in an attempt to increase the understanding of genotype-phenotype correlation for this disorder. The current study summarizes also the spectrum of DUOX2 variations reported to date in the literature. Methods: Two siblings from an nonconsanguineous family with clinical and biochemical criteria suggestive of transient CH were studied. Single-Strand Conformation Polymorphism (SSCP) analysis and sequencing of DNA of TPO and DUOX2 genes were performed. Results: Sequencing analysis of DUOX2 gene revealed two inactivating mutations, a novel c.1057_1058delTT mutation (p.F353Pfs*36, father’s mutation) and a possible previously reported c.1275T>G mutation (p.Y425X, mother’s mutation). Consequently, the two siblings carry a compound heterozygous for p.F353Pfs*36/ p.Y425X mutations, whereas the healthy brother is heterozygous for the c.1275T>G mutation and does not carry the c.1057_1058delTT mutation. Up to date, hundred twenty pathogenic variations and functional single nucleotide polymorphisms in the human DUOX2 gene have been reported associated with transient or permanent CH: 78 missense mutations, 11 nonsense mutations, 26 deletions and insertions, and 6 splice site mutations. The transient or persistent variability of the CH phenotype is not directly related to the number of mutant DUOX2 alleles. Pathogenic DUOX2 mutations were identified together with likely pathogenic variants in the TSHR, DUOXA2, Thyroid peroxidase, Thyroglobulin and SLC26A4 genes. Conclusion: In the present study, we have identified a novel p.F353Pfs*36 mutation in peroxidase like domain of DUOX2 and we have confirmed that total loss of DUOX2 activity by biallelic premature termination codon causes transient CH phenotype.
Fil: Belforte, Fiorella Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Siffo, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Papendieck, Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Enacan, Rosa E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Gruñeiro-Papendieck, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
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
Materia
CONGENITAL HYPOTHYROIDISM
DUOX GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATIONS
PREMATURE STOP CODON
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/51111
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/51111
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature ReviewBelforte, Fiorella SabrinaOlcese, María CeciliaSiffo, SofíaPapendieck, PatriciaEnacan, Rosa E.Gruñeiro-Papendieck, LauraChiesa, Ana ElenaTargovnik, Hector ManuelRivolta, Carina MarcelaCONGENITAL HYPOTHYROIDISMDUOX GENEMUTATIONCOMPOUND HETEROZYGOUS MUTATIONSPREMATURE STOP CODONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose: DUOX2 deficiency is a transient or permanent disorder that results in thyroid dyshormonogenesis. The purpose of this study was to identify and characterize new mutations in the DUOX2 gene in an attempt to increase the understanding of genotype-phenotype correlation for this disorder. The current study summarizes also the spectrum of DUOX2 variations reported to date in the literature. Methods: Two siblings from an nonconsanguineous family with clinical and biochemical criteria suggestive of transient CH were studied. Single-Strand Conformation Polymorphism (SSCP) analysis and sequencing of DNA of TPO and DUOX2 genes were performed. Results: Sequencing analysis of DUOX2 gene revealed two inactivating mutations, a novel c.1057_1058delTT mutation (p.F353Pfs*36, father’s mutation) and a possible previously reported c.1275T>G mutation (p.Y425X, mother’s mutation). Consequently, the two siblings carry a compound heterozygous for p.F353Pfs*36/ p.Y425X mutations, whereas the healthy brother is heterozygous for the c.1275T>G mutation and does not carry the c.1057_1058delTT mutation. Up to date, hundred twenty pathogenic variations and functional single nucleotide polymorphisms in the human DUOX2 gene have been reported associated with transient or permanent CH: 78 missense mutations, 11 nonsense mutations, 26 deletions and insertions, and 6 splice site mutations. The transient or persistent variability of the CH phenotype is not directly related to the number of mutant DUOX2 alleles. Pathogenic DUOX2 mutations were identified together with likely pathogenic variants in the TSHR, DUOXA2, Thyroid peroxidase, Thyroglobulin and SLC26A4 genes. Conclusion: In the present study, we have identified a novel p.F353Pfs*36 mutation in peroxidase like domain of DUOX2 and we have confirmed that total loss of DUOX2 activity by biallelic premature termination codon causes transient CH phenotype.Fil: Belforte, Fiorella Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Siffo, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Papendieck, Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Enacan, Rosa E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Gruñeiro-Papendieck, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: 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; ArgentinaAusting Publishing Group2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/51111Belforte, Fiorella Sabrina; Olcese, María Cecilia; Siffo, Sofía; Papendieck, Patricia; Enacan, Rosa E.; et al.; Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review; Austing Publishing Group; Austin Journal of Allergy; 2; 2; 11-2016; 69-782378-6655CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://austinpublishinggroup.com/allergy/all-issues.phpinfo:eu-repo/semantics/altIdentifier/url/http://austinpublishinggroup.com/thyroid-research/download.php?file=fulltext/thyroids-v2-id1018.pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:38Zoai:ri.conicet.gov.ar:11336/51111instacron: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 09:57:38.818CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
title Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
spellingShingle Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
Belforte, Fiorella Sabrina
CONGENITAL HYPOTHYROIDISM
DUOX GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATIONS
PREMATURE STOP CODON
title_short Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
title_full Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
title_fullStr Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
title_full_unstemmed Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
title_sort Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review
dc.creator.none.fl_str_mv Belforte, Fiorella Sabrina
Olcese, María Cecilia
Siffo, Sofía
Papendieck, Patricia
Enacan, Rosa E.
Gruñeiro-Papendieck, Laura
Chiesa, Ana Elena
Targovnik, Hector Manuel
Rivolta, Carina Marcela
author Belforte, Fiorella Sabrina
author_facet Belforte, Fiorella Sabrina
Olcese, María Cecilia
Siffo, Sofía
Papendieck, Patricia
Enacan, Rosa E.
Gruñeiro-Papendieck, Laura
Chiesa, Ana Elena
Targovnik, Hector Manuel
Rivolta, Carina Marcela
author_role author
author2 Olcese, María Cecilia
Siffo, Sofía
Papendieck, Patricia
Enacan, Rosa E.
Gruñeiro-Papendieck, Laura
Chiesa, Ana Elena
Targovnik, Hector Manuel
Rivolta, Carina Marcela
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CONGENITAL HYPOTHYROIDISM
DUOX GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATIONS
PREMATURE STOP CODON
topic CONGENITAL HYPOTHYROIDISM
DUOX GENE
MUTATION
COMPOUND HETEROZYGOUS MUTATIONS
PREMATURE STOP CODON
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: DUOX2 deficiency is a transient or permanent disorder that results in thyroid dyshormonogenesis. The purpose of this study was to identify and characterize new mutations in the DUOX2 gene in an attempt to increase the understanding of genotype-phenotype correlation for this disorder. The current study summarizes also the spectrum of DUOX2 variations reported to date in the literature. Methods: Two siblings from an nonconsanguineous family with clinical and biochemical criteria suggestive of transient CH were studied. Single-Strand Conformation Polymorphism (SSCP) analysis and sequencing of DNA of TPO and DUOX2 genes were performed. Results: Sequencing analysis of DUOX2 gene revealed two inactivating mutations, a novel c.1057_1058delTT mutation (p.F353Pfs*36, father’s mutation) and a possible previously reported c.1275T>G mutation (p.Y425X, mother’s mutation). Consequently, the two siblings carry a compound heterozygous for p.F353Pfs*36/ p.Y425X mutations, whereas the healthy brother is heterozygous for the c.1275T>G mutation and does not carry the c.1057_1058delTT mutation. Up to date, hundred twenty pathogenic variations and functional single nucleotide polymorphisms in the human DUOX2 gene have been reported associated with transient or permanent CH: 78 missense mutations, 11 nonsense mutations, 26 deletions and insertions, and 6 splice site mutations. The transient or persistent variability of the CH phenotype is not directly related to the number of mutant DUOX2 alleles. Pathogenic DUOX2 mutations were identified together with likely pathogenic variants in the TSHR, DUOXA2, Thyroid peroxidase, Thyroglobulin and SLC26A4 genes. Conclusion: In the present study, we have identified a novel p.F353Pfs*36 mutation in peroxidase like domain of DUOX2 and we have confirmed that total loss of DUOX2 activity by biallelic premature termination codon causes transient CH phenotype.
Fil: Belforte, Fiorella Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Siffo, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Papendieck, Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Enacan, Rosa E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Gruñeiro-Papendieck, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
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
description Purpose: DUOX2 deficiency is a transient or permanent disorder that results in thyroid dyshormonogenesis. The purpose of this study was to identify and characterize new mutations in the DUOX2 gene in an attempt to increase the understanding of genotype-phenotype correlation for this disorder. The current study summarizes also the spectrum of DUOX2 variations reported to date in the literature. Methods: Two siblings from an nonconsanguineous family with clinical and biochemical criteria suggestive of transient CH were studied. Single-Strand Conformation Polymorphism (SSCP) analysis and sequencing of DNA of TPO and DUOX2 genes were performed. Results: Sequencing analysis of DUOX2 gene revealed two inactivating mutations, a novel c.1057_1058delTT mutation (p.F353Pfs*36, father’s mutation) and a possible previously reported c.1275T>G mutation (p.Y425X, mother’s mutation). Consequently, the two siblings carry a compound heterozygous for p.F353Pfs*36/ p.Y425X mutations, whereas the healthy brother is heterozygous for the c.1275T>G mutation and does not carry the c.1057_1058delTT mutation. Up to date, hundred twenty pathogenic variations and functional single nucleotide polymorphisms in the human DUOX2 gene have been reported associated with transient or permanent CH: 78 missense mutations, 11 nonsense mutations, 26 deletions and insertions, and 6 splice site mutations. The transient or persistent variability of the CH phenotype is not directly related to the number of mutant DUOX2 alleles. Pathogenic DUOX2 mutations were identified together with likely pathogenic variants in the TSHR, DUOXA2, Thyroid peroxidase, Thyroglobulin and SLC26A4 genes. Conclusion: In the present study, we have identified a novel p.F353Pfs*36 mutation in peroxidase like domain of DUOX2 and we have confirmed that total loss of DUOX2 activity by biallelic premature termination codon causes transient CH phenotype.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
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/11336/51111
Belforte, Fiorella Sabrina; Olcese, María Cecilia; Siffo, Sofía; Papendieck, Patricia; Enacan, Rosa E.; et al.; Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review; Austing Publishing Group; Austin Journal of Allergy; 2; 2; 11-2016; 69-78
2378-6655
CONICET Digital
CONICET
url http://hdl.handle.net/11336/51111
identifier_str_mv Belforte, Fiorella Sabrina; Olcese, María Cecilia; Siffo, Sofía; Papendieck, Patricia; Enacan, Rosa E.; et al.; Biallelic Stop Codon Mutations (p.F353Pfs*36/p.Y425X) in DUOX2 Gene Associated with Transient Congenital Hypothyroidism: Report of a Family and Literature Review; Austing Publishing Group; Austin Journal of Allergy; 2; 2; 11-2016; 69-78
2378-6655
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://austinpublishinggroup.com/allergy/all-issues.php
info:eu-repo/semantics/altIdentifier/url/http://austinpublishinggroup.com/thyroid-research/download.php?file=fulltext/thyroids-v2-id1018.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Austing Publishing Group
publisher.none.fl_str_mv Austing Publishing Group
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 13.13397

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