A restricted spectrum of NRAS mutations causes Noonan syndrome
Open Access
- 6 December 2009
- journal article
- case report
- Published by Springer Nature in Nature Genetics
- Vol. 42 (1) , 27-29
- https://doi.org/10.1038/ng.497
Abstract
Martin Zenker, Marco Tartaglia, Reza Ahmadian and colleagues report the identification of a restricted spectrum of NRAS mutations in individuals with Noonan syndrome. Functional testing revealed that the mutations confer enhanced stimulus-dependent MAPK activation. Noonan syndrome, a developmental disorder characterized by congenital heart defects, reduced growth, facial dysmorphism and variable cognitive deficits, is caused by constitutional dysregulation of the RAS-MAPK signaling pathway. Here we report that germline NRAS mutations conferring enhanced stimulus-dependent MAPK activation account for some cases of this disorder. These findings provide evidence for an obligate dependency on proper NRAS function in human development and growth.Keywords
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