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

Clin Chim Acta. 2007 Sep;384(1-2):35-40. doi: 10.1016/j.cca.2007.05.016. Epub 2007 May 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Assay
  • Coffin-Lowry Syndrome / diagnosis*
  • Cyclic AMP Response Element-Binding Protein / chemistry*
  • Female
  • Humans
  • Lymphocytes / enzymology*
  • Male
  • Phosphorylation
  • Ribosomal Protein S6 Kinases, 90-kDa / chemistry*


  • Cyclic AMP Response Element-Binding Protein
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3