RSK2 enzymatic assay as a second level diagnostic tool in Coffin-Lowry syndrome

Vanna Micheli, Sylvia Sestini, Veronica Parri, Marco Fichera, Corrado Romano, Francesca Ariani, Ilaria Longo, Francesca Mari, Mirella Bruttini, Alessandra Renieri, Ilaria Meloni

Research output: Contribution to journalArticlepeer-review


Background: Coffin-Lowry syndrome is a semi-dominant condition characterized by severe psychomotor retardation with facial, hand and skeletal malformations resulting from mutations in RSK2 gene, encoding for a serine/threonine kinase. More than 100 different mutations have been identified to date; however, about 50% of clinically diagnosed patients apparently do not have mutations. In order to exclude that these patients have RSK2 mutations missed by standard mutation detection techniques, a rapid and sensitive assay allowing evaluation of RSK2 activity was needed. Methods: RSK2 capacity to phosphorylate a synthetic CREB-peptide in basal and PMA-stimulated conditions was evaluated in lymphoblasts from 3 patients with RSK2 mutations and normal controls. Results: Patients RSK2 activity is normal in nonstimulated conditions but fails to grow following stimulation. The evaluation of the stimulated/non-stimulated activity ratio demonstrated a statistically significant impairment in patients. Conclusions: We have set up an assay which allows the identification of even partial alterations of RSK2 activity and seems to give good results also in females with a balanced X-chromosome inactivation and thus with a presumably normal enzymatic activity in about 50% of cells. Moreover, our data seem to confirm previous reports of a potential direct correlation between the level of RSK2 activity and the severity of cognitive impairment.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalClinica Chimica Acta
Issue number1-2
Publication statusPublished - Sep 2007


  • Coffin Lowry syndrome (CLS)
  • diagnostic tool
  • enzymatic assay
  • RSK2 protein

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry


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