How to cite this article: Cesarini L, Alfieri P, Pantaleoni F, Vasta I, Cerutti M, Petrangeli V, Mariotti P, Leoni C, Ricci D, Vicari S, Selicorni A, Tartaglia M, Mercuri E, Zampino G. 2009. Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade. Am J Med Genet Part A 149A:140–146.
Article first published online: 9 JAN 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 2, pages 140–146, February 2009
How to Cite
Cesarini, L., Alfieri, P., Pantaleoni, F., Vasta, I., Cerutti, M., Petrangeli, V., Mariotti, P., Leoni, C., Ricci, D., Vicari, S., Selicorni, A., Tartaglia, M., Mercuri, E. and Zampino, G. (2009), Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade. Am. J. Med. Genet., 149A: 140–146. doi: 10.1002/ajmg.a.32488
Laura Cesarini and Paolo Alfieri contributed equally to the work.
- Issue published online: 22 JAN 2009
- Article first published online: 9 JAN 2009
- Manuscript Accepted: 27 JUN 2008
- Manuscript Received: 21 FEB 2008
- Telethon-Italy. Grant Number: GGP07115
- Programma di Collaborazione Italia-USA
- cardiofaciocutaneous syndrome;
- Costello syndrome;
- LEOPARD syndrome;
- Noonan syndrome;
- RAS signaling
Mutations in genes coding for transducers participating in the RAS/MAPK pathway have been identified as the molecular cause underlying a group of clinically related developmental disorders with cognitive deficits of variable severity. To determine the spectrum of cognitive defects associated with dysregulation of this signal cascade, we studied the profile of cognitive abilities in patients with mutations affecting the PTPN11, SOS1, HRAS, KRAS, BRAF, RAF1, and MEK1 genes and phenotype–genotype correlations. Our findings support the observation that heterogeneity in cognitive abilities can be at least partially ascribed to the individual affected genes and type of mutation involved. While mutations affecting transducers upstream of RAS were less frequently associated with mental retardation, mutations in downstream components of the pathway were generally associated with a more severe cognitive impairment. Among patients with a heterozygous PTPN11 mutation, the T468M substitution was associated with a mean IQ significantly higher compared to that of individuals carrying the N308D change. Our study provides insights on the range of cognitive abilities in patients with gene mutations causing dysregulation of RAS signaling suggesting that the presence and severity of cognitive involvement can be predicted in part by the gene involved. © 2009 Wiley-Liss, Inc.