Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/58775
Type: Artigo de periódico
Title: RAB23 mutations in carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity
Author: Jenkins, D
Seelow, D
Jehee, FS
Perlyn, CA
Alonso, LG
Bueno, DF
Donnai, D
Josifiova, D
Mathijssen, IMJ
Morton, JEV
Orstavik, KH
Sweeney, E
Wall, SA
Marsh, JL
Nurnberg, P
Passos-Bueno, MR
Wilkie, AOM
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.
Country: EUA
Editor: Univ Chicago Press
Rights: fechado
Identifier DOI: 10.1086/518047
Date Issue: 2007
Appears in Collections:Unicamp - Artigos e Outros Documentos

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