Transcriptional hallmarks of noonan syndrome and noonan-like syndrome with loose anagen hair

Giovanni Battista Ferrero, Gabriele Picco, Giuseppina Baldassarre, Elisabetta Flex, Claudio Isella, Daniela Cantarella, Davide Corà, Nicoletta Chiesa, Nicoletta Crescenzio, Fabio Timeus, Giuseppe Merla, Laura Mazzanti, Giuseppe Zampino, Cesare Rossi, Margherita Silengo, Marco Tartaglia, Enzo Medico

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)703-709
Number of pages7
JournalHuman Mutation
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • Noonan syndrome
  • PTPN11
  • RASopathies
  • SHOC2
  • SOS1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    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., & Medico, E. (2012). Transcriptional hallmarks of noonan syndrome and noonan-like syndrome with loose anagen hair. Human Mutation, 33(4), 703-709. https://doi.org/10.1002/humu.22026