DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome

Detalhes bibliográficos
Autor(a) principal: White, Janson
Data de Publicação: 2015
Outros Autores: Araújo, Juliana Forte Mazzeu de, Hoischen, Alexander, Jhangiani, Shalini N., Gambin, Tomasz, Alcino, Michele Calijorne, Penney, Samantha, Saraiva, Jorge M., Hove, Hanne, Skovby, Flemming, Kayserili, Hu¨lya, Estrella, Elicia, Vulto-van Silfhout, Anneke T., Steehouwer, Marloes, Muzny, Donna M., Sutton, V. Reid, Gibbs, Richard A., Lupski, James R., van Bon, Bregje W.M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/12561
Resumo: Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
id CRUZ_76425ccc8b24f7aac821afdd964beba2
oai_identifier_str oai:www.arca.fiocruz.br:icict/12561
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling White, JansonAraújo, Juliana Forte Mazzeu deHoischen, AlexanderJhangiani, Shalini N.Gambin, TomaszAlcino, Michele CalijornePenney, SamanthaSaraiva, Jorge M.Hove, HanneSkovby, FlemmingKayserili, Hu¨lyaEstrella, EliciaVulto-van Silfhout, Anneke T.Steehouwer, MarloesMuzny, Donna M.Sutton, V. ReidGibbs, Richard A.Lupski, James R.van Bon, Bregje W.M.2016-01-19T17:57:35Z2016-01-19T17:57:35Z2015WHITE, Janson et al. DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome. Am J Hum Genet., vol. 96, n. 4, p. 612-22. 20150002-9297https://www.arca.fiocruz.br/handle/icict/1256110.1016/j.ajhg.2015.02.015engElsevier Inc.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndromeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USAUniversidade Catolica de Brasılia. Programa de Pos-graduaçao em Ciencias Genomicas e Biotecnologia. Brasılia, DF, Brasil/Robinow Syndrome Foundation. Anoka, MN, USARadboud University Medical Center. Radboud Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the NetherlandsBaylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USABaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Warsaw University of Technology. Institute of Computer Science. Warsaw, PolandFundaçao Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, BrasilBaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USACentro Hospitalar e Universitario de Coimbra. Hospital Pediatrico. Medical Genetics Unit. Coimbra, Portugal/University of Coimbra. University Clinic of Pediatrics. Faculty of Medicine. Coimbra, PortugalUniversity of Copenhagen. Rigshospitalet. Department of Clinical Genetics. Copenhagen, DenmarkUniversity of Copenhagen. Rigshospitalet. Department of Clinical Genetics. Copenhagen, DenmarkIstanbul University. Istanbul Medical Faculty. Medical Genetics Department. Istanbul, Turkey/Koc University, Rumelifeneri Yolu. School of Medicine. Medical Genetics Department. Sariyer Istanbul,TurkeyBoston Children’s Hospital and Harvard Medical School. Department of Genetics & Genomics. Boston, MA, USARadboud University Medical Center. Radboud Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the NetherlandsRadboud University Medical Center. Radboud Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the NetherlandsBaylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USABaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/ Texas Children’s Hospital. Houston, TX, USABaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USABaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA/Texas Children’s Hospital. Houston, TX, USA/Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA Han G. BrunnerRadboud University Medical Center. Radboud Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the NetherlandsRobinow syndrome is a genetically heterogeneous disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features and for which both autosomal-recessive and autosomal-dominant inheritance patterns have been described. Causative variants in the non-canonical signaling gene WNT5A underlie a subset of autosomal-dominant Robinow syndrome (DRS) cases, but most individuals with DRS remain without a molecular diagnosis. We performed whole-exome sequencing in four unrelated DRS-affected individuals without coding mutations in WNT5A and found heterozygous DVL1 exon 14 mutations in three of them. Targeted Sanger sequencing in additional subjects with DRS uncovered DVL1 exon 14 mutations in five individuals, including a pair of monozygotic twins. In total, six distinct frameshift mutations were found in eight subjects, and all were heterozygous truncating variants within the penultimate exon of DVL1. In five families in which samples from unaffected parents were available, the variants were demonstrated to represent de novo mutations. All variant alleles are predicted to result in a premature termination codon within the last exon, escape nonsense-mediated decay (NMD), and most likely generate a C-terminally truncated protein with a distinct -1 reading-frame terminus. Study of the transcripts extracted from affected subjects' leukocytes confirmed expression of both wild-type and variant alleles, supporting the hypothesis that mutant mRNA escapes NMD. Genomic variants identified in our study suggest that truncation of the C-terminal domain of DVL1, a protein hypothesized to have a downstream role in the Wnt-5a non-canonical pathway, is a common cause of DRS.Adaptor ProteinsSignal Transducing/geneticsCraniofacial Abnormalities/geneticsFrameshift Mutation/geneticsLimb Deformities, Congenital/geneticsMolecular Sequence DataUrogenital Abnormalities/geneticsinfo: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/12561/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALDVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome..pdfDVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome..pdfapplication/pdf5898265https://www.arca.fiocruz.br/bitstream/icict/12561/2/DVL1%20frameshift%20mutations%20clustering%20in%20the%20penultimate%20exon%20cause%20autosomal-dominant%20Robinow%20syndrome..pdfdf493b901dec9ef841821a825282d1c6MD52TEXTDVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome..pdf.txtDVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome..pdf.txtExtracted texttext/plain11https://www.arca.fiocruz.br/bitstream/icict/12561/3/DVL1%20frameshift%20mutations%20clustering%20in%20the%20penultimate%20exon%20cause%20autosomal-dominant%20Robinow%20syndrome..pdf.txtb308b7fe5c1c2bbdc0cb686d451b84aaMD53icict/125612019-06-19 10:07:08.834oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:07:08Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
title DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
spellingShingle DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
White, Janson
Adaptor Proteins
Signal Transducing/genetics
Craniofacial Abnormalities/genetics
Frameshift Mutation/genetics
Limb Deformities, Congenital/genetics
Molecular Sequence Data
Urogenital Abnormalities/genetics
title_short DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
title_full DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
title_fullStr DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
title_full_unstemmed DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
title_sort DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome
author White, Janson
author_facet White, Janson
Araújo, Juliana Forte Mazzeu de
Hoischen, Alexander
Jhangiani, Shalini N.
Gambin, Tomasz
Alcino, Michele Calijorne
Penney, Samantha
Saraiva, Jorge M.
Hove, Hanne
Skovby, Flemming
Kayserili, Hu¨lya
Estrella, Elicia
Vulto-van Silfhout, Anneke T.
Steehouwer, Marloes
Muzny, Donna M.
Sutton, V. Reid
Gibbs, Richard A.
Lupski, James R.
van Bon, Bregje W.M.
author_role author
author2 Araújo, Juliana Forte Mazzeu de
Hoischen, Alexander
Jhangiani, Shalini N.
Gambin, Tomasz
Alcino, Michele Calijorne
Penney, Samantha
Saraiva, Jorge M.
Hove, Hanne
Skovby, Flemming
Kayserili, Hu¨lya
Estrella, Elicia
Vulto-van Silfhout, Anneke T.
Steehouwer, Marloes
Muzny, Donna M.
Sutton, V. Reid
Gibbs, Richard A.
Lupski, James R.
van Bon, Bregje W.M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv White, Janson
Araújo, Juliana Forte Mazzeu de
Hoischen, Alexander
Jhangiani, Shalini N.
Gambin, Tomasz
Alcino, Michele Calijorne
Penney, Samantha
Saraiva, Jorge M.
Hove, Hanne
Skovby, Flemming
Kayserili, Hu¨lya
Estrella, Elicia
Vulto-van Silfhout, Anneke T.
Steehouwer, Marloes
Muzny, Donna M.
Sutton, V. Reid
Gibbs, Richard A.
Lupski, James R.
van Bon, Bregje W.M.
dc.subject.en.pt_BR.fl_str_mv Adaptor Proteins
Signal Transducing/genetics
Craniofacial Abnormalities/genetics
Frameshift Mutation/genetics
Limb Deformities, Congenital/genetics
Molecular Sequence Data
Urogenital Abnormalities/genetics
topic Adaptor Proteins
Signal Transducing/genetics
Craniofacial Abnormalities/genetics
Frameshift Mutation/genetics
Limb Deformities, Congenital/genetics
Molecular Sequence Data
Urogenital Abnormalities/genetics
description Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2016-01-19T17:57:35Z
dc.date.available.fl_str_mv 2016-01-19T17:57:35Z
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 WHITE, Janson et al. DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome. Am J Hum Genet., vol. 96, n. 4, p. 612-22. 2015
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/12561
dc.identifier.issn.none.fl_str_mv 0002-9297
dc.identifier.doi.none.fl_str_mv 10.1016/j.ajhg.2015.02.015
identifier_str_mv WHITE, Janson et al. DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome. Am J Hum Genet., vol. 96, n. 4, p. 612-22. 2015
0002-9297
10.1016/j.ajhg.2015.02.015
url https://www.arca.fiocruz.br/handle/icict/12561
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 Elsevier Inc.
publisher.none.fl_str_mv Elsevier Inc.
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/12561/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/12561/2/DVL1%20frameshift%20mutations%20clustering%20in%20the%20penultimate%20exon%20cause%20autosomal-dominant%20Robinow%20syndrome..pdf
https://www.arca.fiocruz.br/bitstream/icict/12561/3/DVL1%20frameshift%20mutations%20clustering%20in%20the%20penultimate%20exon%20cause%20autosomal-dominant%20Robinow%20syndrome..pdf.txt
bitstream.checksum.fl_str_mv 5a560609d32a3863062d77ff32785d58
df493b901dec9ef841821a825282d1c6
b308b7fe5c1c2bbdc0cb686d451b84aa
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1798324657914380288

Registros relacionados