RAB23 mutations in carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity

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dc.contributor.author Jenkins, Dagan
dc.contributor.author Seelow, Dominik
dc.contributor.author Jehee, Fernanda S.
dc.contributor.author Perlyn, Chad A.
dc.contributor.author Alonso, Luis Garcia [UNIFESP]
dc.contributor.author Bueno, Daniela F.
dc.contributor.author Donnai, Dian
dc.contributor.author Josifiova, Dragana
dc.contributor.author Mathijssen, Irene M. J.
dc.contributor.author Morton, Jenny E. V.
dc.contributor.author Orstavik, Karen Helene
dc.contributor.author Sweeney, Elizabeth
dc.contributor.author Wall, Steven A.
dc.contributor.author Marsh, Jeffrey L.
dc.contributor.author Nurnberg, Peter
dc.contributor.author Passos-Bueno, Maria Rita
dc.contributor.author Wilkie, Andrew O. M.
dc.date.accessioned 2016-01-24T13:48:44Z
dc.date.available 2016-01-24T13:48:44Z
dc.date.issued 2007-06-01
dc.identifier http://dx.doi.org/10.1086/518047
dc.identifier.citation American Journal of Human Genetics. Chicago: Univ Chicago Press, v. 80, n. 6, p. 1162-1170, 2007.
dc.identifier.issn 0002-9297
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/29763
dc.description.abstract Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. in 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. the discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis-an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components-and provides a new molecular target for studies of obesity. en
dc.format.extent 1162-1170
dc.language.iso eng
dc.publisher Univ Chicago Press
dc.relation.ispartof American Journal of Human Genetics
dc.rights Acesso aberto
dc.title RAB23 mutations in carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity en
dc.type Artigo
dc.contributor.institution Univ Oxford
dc.contributor.institution Oxford Radcliffe Hosp
dc.contributor.institution Univ Cologne
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Universidade Estadual de Campinas (UNICAMP)
dc.contributor.institution Washington Univ
dc.contributor.institution St Johns Mercy Med Ctr
dc.contributor.institution Univ Manchester
dc.contributor.institution Guys Hosp
dc.contributor.institution Erasmus MC
dc.contributor.institution Womens Hosp Med Ctr
dc.contributor.institution Univ Oslo
dc.description.affiliation Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England
dc.description.affiliation Oxford Radcliffe Hosp, Craniofacial Unit, Natl Hlth Serv Trust, Oxford, England
dc.description.affiliation Univ Cologne, Cologne Ctr Genom, Cologne, Germany
dc.description.affiliation Univ Cologne, Inst Genet, D-5000 Cologne, Germany
dc.description.affiliation Univ São Paulo, Ctr Estudos Genoma Humano, Dept Biol, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Morfol, São Paulo, Brazil
dc.description.affiliation Univ Estadual Campinas, SOBRAPAR, São Paulo, Brazil
dc.description.affiliation Washington Univ, Sch Med, Div Plast Surg, St Louis, MO 63110 USA
dc.description.affiliation St Johns Mercy Med Ctr, Cleft Lip Palate & Craniofacial Deform Ctr, St Louis, MO 63141 USA
dc.description.affiliation Univ Manchester, St Marys Hosp, Acad Unit Med Genet, Manchester M13 0JH, Lancs, England
dc.description.affiliation Guys Hosp, London SE1 9RT, England
dc.description.affiliation Erasmus MC, Dept Plast & Reconstruct Surg, Rotterdam, Netherlands
dc.description.affiliation Womens Hosp Med Ctr, W Midlands Reg Genet Serv, Birmingham, W Midlands, England
dc.description.affiliation Univ Oslo, Rikshosp, Dept Med Genet, Radiumhosp,Med Ctr, N-0027 Oslo, Norway
dc.description.affiliation Univ Oslo, Rikshosp, Fac Div, N-0027 Oslo, Norway
dc.description.affiliation Womens Hosp Med Ctr, Merseyside & Cheshire Clin Genet Serv, Liverpool, Merseyside, England
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Morfol, São Paulo, Brazil
dc.identifier.file WOS000246553800014.pdf
dc.identifier.doi 10.1086/518047
dc.description.source Web of Science
dc.identifier.wos WOS:000246553800014


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