Communicated by Nancy B. Spinner
Transcriptional hallmarks of noonan syndrome and noonan-like syndrome with loose anagen hair†
Article first published online: 14 FEB 2012
© 2012 Wiley Periodicals, Inc.
Special Issue: Focus on the NIH Undiagnosed Diseases Program
Volume 33, Issue 4, pages 703–709, April 2012
How to Cite
Ferrero, G. B., Picco, G., Baldassarre, G., Flex, E., Isella, C., Cantarella, D., Corà, D., Chiesa, N., Crescenzio, N., Timeus, F., Merla, G., Mazzanti, L., Zampino, G., Rossi, C., Silengo, M., Tartaglia, M. and Medico, E. (2012), Transcriptional hallmarks of noonan syndrome and noonan-like syndrome with loose anagen hair. Hum. Mutat., 33: 703–709. doi: 10.1002/humu.22026
- Issue published online: 12 MAR 2012
- Article first published online: 14 FEB 2012
- Accepted manuscript online: 17 JAN 2012 12:00AM EST
- Manuscript Accepted: 4 JAN 2012
- Manuscript Received: 9 AUG 2011
- AIRC (IG9127); Regione Piemonte (e-LAB, PRESTO); FPRC-ONLUS (5×1000 2008); Telethon-Italy (GGP10020); ERA-Net (NSEuroNet); Convenzione Italia-USA 2010 (11US/10); Compagnia di San Paolo
- Noonan syndrome;
Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS is genetically heterogeneous, being caused by germline mutations affecting various genes implicated in the RAS signaling network. This network transduces extracellular signals into intracellular biochemical and transcriptional responses controlling cell proliferation, differentiation, metabolism, and senescence. To explore the transcriptional consequences of NS-causing mutations, we performed global mRNA expression profiling on peripheral blood mononuclear cells obtained from 23 NS patients carrying heterozygous mutations in PTPN11 or SOS1. Gene expression profiling was also resolved in five subjects with Noonan-like syndrome with loose anagen hair (NS/LAH), a condition clinically related to NS and caused by an invariant mutation in SHOC2. Robust transcriptional signatures were found to specifically discriminate each of the three mutation groups from 21 age- and sex-matched controls. Despite the only partial overlap in terms of gene composition, the three signatures showed a notable concordance in terms of biological processes and regulatory circuits affected. These data establish expression profiling of peripheral blood mononuclear cells as a powerful tool to appreciate differential perturbations driven by germline mutations of transducers involved in RAS signaling and to dissect molecular mechanisms underlying NS and other RASopathies. Hum Mutat 33:703–709, 2012. © 2012 Wiley Periodicals, Inc.