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

Abstract

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.

• Authors: Vanna Micheli, Sylvia Sestini, Veronica Parri, Marco Fichera, Corrado Romano, Francesca Ariani, Ilaria Longo, Francesca Mari, Mirella Bruttini, Alessandra Renieri, Ilaria Meloni
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 384 Issue 1-2 Pg. 35-40 (Sep 2007) ISSN: 0009-8981 [Print] Netherlands
• PMID: 17586481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)