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Mutation of the LUNATIC FRINGE gene in humans Causes spondylocostal dysostosis with a severe vertebral phenotype

Sparrow, D. B., Chapman, G., Wouters, M. A., Whittock, N. V., Ellard, S., Fatkin, D., Turnpenny, P. D., Kusumi, K., Sillence, D. and Dunwoodie, S. L. 2006, Mutation of the LUNATIC FRINGE gene in humans Causes spondylocostal dysostosis with a severe vertebral phenotype, American journal of human genetics, vol. 78, no. 1, pp. 28-37, doi: 10.1086/498879.

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Title Mutation of the LUNATIC FRINGE gene in humans Causes spondylocostal dysostosis with a severe vertebral phenotype
Author(s) Sparrow, D. B.
Chapman, G.
Wouters, M. A.
Whittock, N. V.
Ellard, S.
Fatkin, D.
Turnpenny, P. D.
Kusumi, K.
Sillence, D.
Dunwoodie, S. L.
Journal name American journal of human genetics
Volume number 78
Issue number 1
Start page 28
End page 37
Publisher Cell Press
Place of publication Cambridge, Ma.
Publication date 2006-01
ISSN 0002-9297
1537-6605
Summary The spondylocostal dysostoses (SCDs) are a heterogeneous group of vertebral malsegmentation disorders that arise during embryonic development by a disruption of somitogenesis. Previously, we had identified two genes that cause a subset of autosomal recessive forms of this disease: DLL3 (SCD1) and MESP2 (SCD2). These genes are important components of the Notch signaling pathway, which has multiple roles in development and disease. Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD. LFNG encodes a glycosyltransferase that modifies the Notch family of cell-surface receptors, a key step in the regulation of this signaling pathway. A missense mutation was identified in a highly conserved phenylalanine close to the active site of the enzyme. Functional analysis revealed that the mutant LFNG was not localized to the correct compartment of the cell, was unable to modulate Notch signaling in a cell-based assay, and was enzymatically inactive. This represents the first known mutation in the human LFNG gene and reinforces the hypothesis that proper regulation of the Notch signaling pathway is an absolute requirement for the correct patterning of the axial skeleton.
Language eng
DOI 10.1086/498879
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2005, Elsevier
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30038985

Document type: Journal Article
Collections: School of Life and Environmental Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.