A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3

Detalhes bibliográficos
Autor(a) principal: Carvalho, Flavia M.
Data de Publicação: 2016
Outros Autores: Poletta, Fernando A., Castilla, Eduardo E., Múltipla autoria - ver em Notas
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/29577
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil.
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spelling Carvalho, Flavia M.Poletta, Fernando A.Castilla, Eduardo E.Múltipla autoria - ver em Notas2018-10-16T16:41:30Z2018-10-16T16:41:30Z2016LESLIE, Elizabeth J. et al. A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3. The American Journal of Human Genetics, v.98, p.744–754, April 2016.0002-9297 .https://www.arca.fiocruz.br/handle/icict/2957710.1016/j.ajhg.2016.02.014engThe American Society of Human GeneticsFissura palatinaEstudo associativofissura palatina não sindrômicaGRHL3defeito de nasçencaCleft Palateassociation studybirth defectGRHL3nonsyndromic CPA Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil.Múltipla autoria - ver em NotasCleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p ¼ 4.08 3 10 9) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR ¼ 8.3, 95% CI 4.1–16.8; OR ¼ 2.16, 95% CI 1.43–3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.info: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/29577/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALflaviam_carvalho_etal_IOC_2016.pdfflaviam_carvalho_etal_IOC_2016.pdfapplication/pdf1047761https://www.arca.fiocruz.br/bitstream/icict/29577/2/flaviam_carvalho_etal_IOC_2016.pdf9b384effb43639a6b6b27b10406c7a2dMD52TEXTflaviam_carvalho_etal_IOC_2016.pdf.txtflaviam_carvalho_etal_IOC_2016.pdf.txtExtracted texttext/plain59068https://www.arca.fiocruz.br/bitstream/icict/29577/3/flaviam_carvalho_etal_IOC_2016.pdf.txtf03a5e24fa551af74fa3cfd10a835ca6MD53icict/295772022-06-24 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dc.title.pt_BR.fl_str_mv A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
title A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
spellingShingle A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
Carvalho, Flavia M.
Fissura palatina
Estudo associativo
fissura palatina não sindrômica
GRHL3
defeito de nasçenca
Cleft Palate
association study
birth defect
GRHL3
nonsyndromic CP
title_short A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
title_full A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
title_fullStr A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
title_full_unstemmed A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
title_sort A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3
author Carvalho, Flavia M.
author_facet Carvalho, Flavia M.
Poletta, Fernando A.
Castilla, Eduardo E.
Múltipla autoria - ver em Notas
author_role author
author2 Poletta, Fernando A.
Castilla, Eduardo E.
Múltipla autoria - ver em Notas
author2_role author
author
author
dc.contributor.author.fl_str_mv Carvalho, Flavia M.
Poletta, Fernando A.
Castilla, Eduardo E.
Múltipla autoria - ver em Notas
dc.subject.other.pt_BR.fl_str_mv Fissura palatina
Estudo associativo
fissura palatina não sindrômica
GRHL3
defeito de nasçenca
topic Fissura palatina
Estudo associativo
fissura palatina não sindrômica
GRHL3
defeito de nasçenca
Cleft Palate
association study
birth defect
GRHL3
nonsyndromic CP
dc.subject.en.pt_BR.fl_str_mv Cleft Palate
association study
birth defect
GRHL3
nonsyndromic CP
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil.
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2018-10-16T16:41:30Z
dc.date.available.fl_str_mv 2018-10-16T16:41:30Z
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 LESLIE, Elizabeth J. et al. A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3. The American Journal of Human Genetics, v.98, p.744–754, April 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/29577
dc.identifier.issn.pt_BR.fl_str_mv 0002-9297 .
dc.identifier.eissn.none.fl_str_mv 10.1016/j.ajhg.2016.02.014
identifier_str_mv LESLIE, Elizabeth J. et al. A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3. The American Journal of Human Genetics, v.98, p.744–754, April 2016.
0002-9297 .
10.1016/j.ajhg.2016.02.014
url https://www.arca.fiocruz.br/handle/icict/29577
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 The American Society of Human Genetics
publisher.none.fl_str_mv The American Society of Human Genetics
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/29577/1/license.txt
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