Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.

The Coffin-Lowry syndrome (CLS) is a rare X-linked semidominant syndrome characterized by severe psychomotor retardation, facial dysmorphism, digit abnormalities and progressive skeletal deformations. CLS is caused by mutations in a gene located in Xp22.2, RPS6KA3. This gene encodes for a growth factor-regulated serine/threonine protein kinase, RSK2 (ribosomal S6 kinase 2), acting in the Ras-mitogen-activated protein kinase signaling pathway. Mutations in the RPS6KA3 gene are extremely heterogeneous and lead to premature termination of translation and/or to loss of phosphotransferase activity of the RSK2 protein. Screening for RSK2 mutations is essential in most cases to confirm the diagnosis as well as for genetic counseling. Here we present 44 novel mutations in RSK2 causing CLS. The overall number of CLS mutations reported now is 128. Thirty-three percent of mutations are missense mutations, 15% nonsense mutations, 20% splicing errors and 29% short deletion or insertion events. Only four large deletions have so far been found. They are distributed throughout the RPS6KA3 gene, and the majority has been found in a single family. This study further confirms the high rate of new mutations at the RSK2 locus. It is important to consider the possibility of mosaicism when providing genetic counseling in CLS families.

Integration architecture: the ISAR project.

ISAR (Integration System Architecture) will integrate six AIM Projects on the HIS platform at the University Hospital (CHRU) of LILLE. These Projects were elicited from six European consortiums that provided prototypes or pre-competitive products. These consortia are: ESTEEM (storage and analysis of electromyograms), EURIPACS (picture archiving and communication system), MENELAS (analysis of the natural language for medical applications), OEDIPE (storage and serial analysis of electrocardiograms), OPADE (help with drug prescription), and TANIT (mobile system for anaesthesia). When introducing an information system to a medical department and running it, two issues arise. First, how can the Information system be anchored to the Clinical processes in order to support them in an effective and efficient way, and, second, how can the Information system adapt to the changes in the Clinical processes?