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

Giuseppe Zampino, Marco Tartaglia, 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, Cesare Rossi, Margherita Silengo, Enzo Medico

Risultato della ricerca: Contributo in rivistaArticolo in rivista

5 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)703-709
Numero di pagine7
RivistaHuman Mutation
Volume33
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukocytes, Mononuclear
  • Male
  • Mutation
  • Noonan Syndrome
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • SOS1 Protein
  • Signal Transduction
  • Transcription, Genetic
  • ras Proteins

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