Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations

Detalhes bibliográficos
Autor(a) principal: Ramos, Helton Estrela
Data de Publicação: 2014
Outros Autores: Carré, A, Chevrier, L, Szinnai, G, Tron, E, Cerqueira, Taíse Lima de Oliveira, Léger, J, Cabrol, S, Puel, O, Queinnec, C, De Roux, N, Guillot, L, Castanet, M, Polak, M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/19036
Resumo: Electricité de France (RB 200605), the European Society for Paediatric Endocrinology (ESPE) Research Unit (M Polak), Fondation Grace de Monaco and PHRC 2011 Hypotygen sponsored by the French Ministry, SFE (Société française d’endocrinologie) MercK Serono grant (M Castanet), Fapesb (Fundação de Amparo à Pesquisa no Estado da Bahia), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).
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spelling Ramos, Helton EstrelaCarré, AChevrier, LSzinnai, GTron, ECerqueira, Taíse Lima de OliveiraLéger, JCabrol, SPuel, OQueinnec, CDe Roux, NGuillot, LCastanet, MPolak, M2017-05-29T17:28:58Z2017-05-29T17:28:58Z2014RAMOS, H. E. et al. Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations. European Journal of Endocrinology, v. 171, p. 499–507, 2014.0804-4643https://www.arca.fiocruz.br/handle/icict/1903610.1530/EJE-13-1006Electricité de France (RB 200605), the European Society for Paediatric Endocrinology (ESPE) Research Unit (M Polak), Fondation Grace de Monaco and PHRC 2011 Hypotygen sponsored by the French Ministry, SFE (Société française d’endocrinologie) MercK Serono grant (M Castanet), Fapesb (Fundação de Amparo à Pesquisa no Estado da Bahia), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).Université Paris Descartes. INSERM. Sorbonne Paris Cité. Paris, France / Hôpital Necker Enfants-Malades. Centre des Maladies Endocriniennes Rares de la Croissance. Pediatric Endocrine, Gynecology and Diabetes Unit. Paris, France / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilUniversité Paris Descartes. INSERM. Sorbonne Paris Cité. Paris, France / Hôpital Necker Enfants-Malades. Centre des Maladies Endocriniennes Rares de la Croissance. Pediatric Endocrine, Gynecology and Diabetes Unit. Paris, France / IMAGINE Institute. Paris, FranceParis Diderot University. INSERM. Robert Debré Hospital. Paris, FranceUniversité Paris Descartes. INSERM. Sorbonne Paris Cité. Paris, France / Hôpital Necker Enfants-Malades. Centre des Maladies Endocriniennes Rares de la Croissance. Pediatric Endocrine, Gynecology and Diabetes Unit. Paris, France / IMAGINE Institute. Paris, FranceUniversity Basel. University Children’s Hospital Basel. Pediatric Endocrinology. Basel, SwitzerlandUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHôpital Armand Trousseau. Pediatric Endocrine Unit. Paris, FranceHôpital Armand Trousseau. Pediatric Endocrine Unit. Paris, FranceCHU. Pediatrics Department. Bordeaux, FranceCH de Cornouailles-Hopital Laennec. Pediatrics Department. Quimper, FranceParis Diderot University. INSERM. Robert Debré Hospital. Paris, FranceUniversité Pierre-et-Marie Curie. INSERM. Saint-Antonie Hospital. Saint-Antoine Research Center. Paris, FranceUniversité Paris Descartes. INSERM. Sorbonne Paris Cité. Paris, France / Hôpital Necker Enfants-Malades. Centre des Maladies Endocriniennes Rares de la Croissance. Pediatric Endocrine, Gynecology and Diabetes Unit. Paris, France / University Hospital of Rouen. Pediatrics Department. CH Charles Nicolle. Rouen, FranceUniversité Paris Descartes. INSERM. Sorbonne Paris Cité. Paris, France / Hôpital Necker Enfants-Malades. Centre des Maladies Endocriniennes Rares de la Croissance. Pediatric Endocrine, Gynecology and Diabetes Unit. Paris, France / IMAGINE Institute. Paris, FranceWithin the last two decades, heterozygous loss-of-function PAX8 mutations have been reported in patients with a wide degree of thyroid gland dysfunction and growth despite the presence of identical mutations. Objectives: To search for PAX8 mutations in a cohort of patients with congenital hypothyroidism (CH) and various types of thyroid gland defects. Design: A cross-sectional study was conducted in a cohort of patients. Setting: The French neonatal screening program was used for recruiting patients. Patients: A total of 118 patients with CH, including 45 with familial and 73 with sporadic diseases, were included in this study. The thyroid gland was normal in 23 patients had hypoplasia, 25 had hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy. Results: We found four different PAX8 mutations (p.R31C, p.R31H, p.R108X, and p.I47T) in ten patients (six patients with CH and four family members), two with sporadic and eight with familial diseases. Imaging studies performed in the index cases showed ectopic thyroid gland (nZ2), hypoplasia (nZ2), eutopic lobar asymmetry (nZ1), and eutopic gland compatible with dyshormonogenesis (nZ1). The previously reported p.R31C and the novel p.I47T PAX8 mutations are devoid of activity. Conclusion: Four different PAX8 mutations were detected in six index patients with CH (ten total subjects). The p.R31C, p.R31H, and p.R108X mutations have been reported. The novel p.I47T PAX8 mutation presented loss of function leading to CH. Thyroid ectopy was observed in two cases of PAX8 (p.R31H) mutation, a finding that has not been reported previously. We observed a high inter-individual and intra-familial variability of the phenotype in PAX8 mutations, underlining that population genetic studies for CH should include patients with various clinical presentationsengBio Scientifica / European Society of EndocrinologyHipotireoidismoGlândula tireóideMutaçãoMutagêneseHumanosHypothyroidismThyroid glandMutationThyroid DysgenesisMutagenesisHumansHipotireoidismoGlândula tireóideMutagêneseHumanosExtreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/19036/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALRamos HE Extreme phenotypic 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dc.title.pt_BR.fl_str_mv Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
title Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
spellingShingle Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
Ramos, Helton Estrela
Hipotireoidismo
Glândula tireóide
Mutação
Mutagênese
Humanos
Hypothyroidism
Thyroid gland
Mutation
Thyroid Dysgenesis
Mutagenesis
Humans
Hipotireoidismo
Glândula tireóide
Mutagênese
Humanos
title_short Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
title_full Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
title_fullStr Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
title_full_unstemmed Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
title_sort Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations
author Ramos, Helton Estrela
author_facet Ramos, Helton Estrela
Carré, A
Chevrier, L
Szinnai, G
Tron, E
Cerqueira, Taíse Lima de Oliveira
Léger, J
Cabrol, S
Puel, O
Queinnec, C
De Roux, N
Guillot, L
Castanet, M
Polak, M
author_role author
author2 Carré, A
Chevrier, L
Szinnai, G
Tron, E
Cerqueira, Taíse Lima de Oliveira
Léger, J
Cabrol, S
Puel, O
Queinnec, C
De Roux, N
Guillot, L
Castanet, M
Polak, M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ramos, Helton Estrela
Carré, A
Chevrier, L
Szinnai, G
Tron, E
Cerqueira, Taíse Lima de Oliveira
Léger, J
Cabrol, S
Puel, O
Queinnec, C
De Roux, N
Guillot, L
Castanet, M
Polak, M
dc.subject.other.pt_BR.fl_str_mv Hipotireoidismo
Glândula tireóide
Mutação
Mutagênese
Humanos
topic Hipotireoidismo
Glândula tireóide
Mutação
Mutagênese
Humanos
Hypothyroidism
Thyroid gland
Mutation
Thyroid Dysgenesis
Mutagenesis
Humans
Hipotireoidismo
Glândula tireóide
Mutagênese
Humanos
dc.subject.en.pt_BR.fl_str_mv Hypothyroidism
Thyroid gland
Mutation
Thyroid Dysgenesis
Mutagenesis
Humans
dc.subject.decs.pt_BR.fl_str_mv Hipotireoidismo
Glândula tireóide
Mutagênese
Humanos
description Electricité de France (RB 200605), the European Society for Paediatric Endocrinology (ESPE) Research Unit (M Polak), Fondation Grace de Monaco and PHRC 2011 Hypotygen sponsored by the French Ministry, SFE (Société française d’endocrinologie) MercK Serono grant (M Castanet), Fapesb (Fundação de Amparo à Pesquisa no Estado da Bahia), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2017-05-29T17:28:58Z
dc.date.available.fl_str_mv 2017-05-29T17:28:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv RAMOS, H. E. et al. Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations. European Journal of Endocrinology, v. 171, p. 499–507, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/19036
dc.identifier.issn.pt_BR.fl_str_mv 0804-4643
dc.identifier.doi.none.fl_str_mv 10.1530/EJE-13-1006
identifier_str_mv RAMOS, H. E. et al. Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations. European Journal of Endocrinology, v. 171, p. 499–507, 2014.
0804-4643
10.1530/EJE-13-1006
url https://www.arca.fiocruz.br/handle/icict/19036
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Bio Scientifica / European Society of Endocrinology
publisher.none.fl_str_mv Bio Scientifica / European Society of Endocrinology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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instacron_str FIOCRUZ
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collection Repositório Institucional da FIOCRUZ (ARCA)
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