RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1797059090576310272 |
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| author | Jenkins, D Seelow, D Jehee, F Perlyn, C Alonso, L Bueno, D Donnai, D Josifova, D Josifiova, D Mathijssen, I Morton, J Orstavik, K Sweeney, E Wall, SA Marsh, J Nurnberg, P Passos-Bueno, MR Wilkie, A |
| author_facet | Jenkins, D Seelow, D Jehee, F Perlyn, C Alonso, L Bueno, D Donnai, D Josifova, D Josifiova, D Mathijssen, I Morton, J Orstavik, K Sweeney, E Wall, SA Marsh, J Nurnberg, P Passos-Bueno, MR Wilkie, A |
| author_sort | Jenkins, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:59:21Z |
| format | Journal article |
| id | oxford-uuid:26ba825f-edf9-4b85-9999-3295b5f6cbc7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:59:21Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:26ba825f-edf9-4b85-9999-3295b5f6cbc72022-03-26T12:02:44ZRAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:26ba825f-edf9-4b85-9999-3295b5f6cbc7EnglishSymplectic Elements at Oxford2007Jenkins, DSeelow, DJehee, FPerlyn, CAlonso, LBueno, DDonnai, DJosifova, DJosifiova, DMathijssen, IMorton, JOrstavik, KSweeney, EWall, SAMarsh, JNurnberg, PPassos-Bueno, MRWilkie, ACarpenter 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. |
| spellingShingle | Jenkins, D Seelow, D Jehee, F Perlyn, C Alonso, L Bueno, D Donnai, D Josifova, D Josifiova, D Mathijssen, I Morton, J Orstavik, K Sweeney, E Wall, SA Marsh, J Nurnberg, P Passos-Bueno, MR Wilkie, A RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. |
| title | RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. |
| title_full | RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. |
| title_fullStr | RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. |
| title_full_unstemmed | RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. |
| title_short | RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. |
| title_sort | rab23 mutations in carpenter syndrome imply an unexpected role for hedgehog signaling in cranial suture development and obesity |
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