| Author | Carvalho, Flavia M. | |
| Author | Poletta, Fernando A. | |
| Author | Castilla, Eduardo E. | |
| Author | Múltipla autoria - ver em Notas | |
| Access date | 2018-10-16T16:41:30Z | |
| Available date | 2018-10-16T16:41:30Z | |
| Document date | 2016 | |
| Citation | 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. | pt_BR |
| ISSN | 0002-9297 . | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/29577 | |
| Language | eng | pt_BR |
| Publisher | The American Society of Human Genetics | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Fissura palatina | pt_BR |
| Subject in Portuguese | Estudo associativo | pt_BR |
| Subject in Portuguese | fissura palatina não sindrômica | pt_BR |
| Subject in Portuguese | GRHL3 | pt_BR |
| Subject in Portuguese | defeito de nasçenca | pt_BR |
| Title | A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3 | pt_BR |
| Type | Article | pt_BR |
| Abstract | Cleft 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratóri de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Múltipla autoria - ver em Notas | pt_BR |
| Subject | Cleft Palate | pt_BR |
| Subject | association study | pt_BR |
| Subject | birth defect | pt_BR |
| Subject | GRHL3 | pt_BR |
| Subject | nonsyndromic CP | pt_BR |
| e-ISSN | 10.1016/j.ajhg.2016.02.014 | |
