Journal article

Heterozygous germline mutations in the CBL tumor-suppressor gene cause a noonan syndrome-like phenotype

S Martinelli, A De Luca, E Stellacci, C Rossi, S Checquolo, F Lepri, V Caputo, M Silvano, F Buscherini, F Consoli, G Ferrara, MC Digilio, ML Cavaliere, JM Van Hagen, G Zampino, I Van Der Burgt, GB Ferrero, L Mazzanti, I Screpanti, HG Yntema Show all

American Journal of Human Genetics | CELL PRESS | Published : 2010

Abstract

RAS signaling plays a key role in controlling appropriate cell responses to extracellular stimuli and participates in early and late developmental processes. Although enhanced flow through this pathway has been established as a major contributor to oncogenesis, recent discoveries have revealed that aberrant RAS activation causes a group of clinically related developmental disorders characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, ectodermal and musculoskeletal anomalies, and increased risk for certain malignancies. Here, we report that heterozygous germline mutations in CBL, a tumor-suppressor gene that is mutated in myeloi..

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University of Melbourne Researchers

Grants

Awarded by National Institutes of Health


Funding Acknowledgements

We are indebted to the patients and families who participated in the study, the physicians who referred the subjects, Serenella Venanzi (Istituto Superiore di Sanita, Rome, Italy) for experimental support, and Paolo Bazzicalupo and Elia Di Schiavi (Istituto di Genetica e Biofisica "A. Buzzati Traverso," Consiglio Nazionale delle Ricerche, Naples, Italy) for stimulating discussions. This research was funded by grants from Telethon-Italy (GGP10020) and "Associazione Italiana Sindromi di Costello e Cardiofaciocutanea" to M.T., from ERA-Net for research programmes on rare diseases 2009 (European network on Noonan Syndrome and related disorders) to M.T. and M.Z., from the Italian Ministry of Health (RC2010) to F.L., and from the National Institutes of Health (HL71207) and March of Dimes (FY 07-286) to B.D.G.