Journal article
Carpenter syndrome: Extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay
Human Mutation, Vol.32(4), pp.E2069-E2078
2011
Abstract
Carpenter syndrome, a rare autosomal recessive disorder characterized by a combination of craniosynostosis, polysyndactyly, obesity, and other congenital malformations, is caused by mutations in RAB23, encoding a member of the Rab-family of small GTPases. In 15 out of 16 families previously reported, the disease was caused by homozygosity for truncating mutations, and currently only a single missense mutation has been identified in a compound heterozygote. Here, we describe a further 8 independent families comprising 10 affected individuals with Carpenter syndrome, who were positive for mutations in RAB23. We report the first homozygous missense mutation and in-frame deletion, highlighting key residues for RAB23 function, as well as the first splice-site mutation. Multi-suture craniosynostosis and polysyndactyly have been present in all patients described to date, and abnormal external genitalia have been universal in boys. High birth weight was not evident in the current group of patients, but further evidence for laterality defects is reported. No genotype-phenotype correlations are apparent. We provide experimental evidence that transcripts encoding truncating mutations are subject to nonsense-mediated decay, and that this plays an important role in the pathogenesis of many RAB23 mutations. These observations refine the phenotypic spectrum of Carpenter syndrome and offer new insights into molecular pathogenesis
Details
- Title
- Carpenter syndrome: Extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay
- Authors/Creators
- D. Jenkins (Author/Creator)G. Baynam (Author/Creator)L. De Catte (Author/Creator)N. Elcioglu (Author/Creator)M.T. Gabbett (Author/Creator)L. Hudgins (Author/Creator)J.A. Hurst (Author/Creator)F.S. Jehee (Author/Creator)C. Oley (Author/Creator)A.O.M. Wilkie (Author/Creator)
- Publication Details
- Human Mutation, Vol.32(4), pp.E2069-E2078
- Publisher
- John Wiley & Sons Inc.
- Identifiers
- 991005542134207891
- Copyright
- © 2011 Wiley-Liss, Inc.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
165 File views/ downloads
55 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.132 Extracellular Matrix & Cell Differentiation
- 1.132.1265 Craniosynostosis & FGFR
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics