Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. CLS is caused by mutations in the RPS6KA3 gene located at Xp22.2, which encodes RSK2, a growth-factor-regulated protein kinase. RPS6KA3 mutations are extremely heterogeneous and lead to loss of phosphotransferase activity in the RSK2 kinase, most often because of premature termination of translation.

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.

P3 is an HIV-2/SIV ancestral peptide with low antigenicity, high stability, and potent activity against both HIV-1, including variants resistant to T-20, and HIV-2. Similar evolutionary biology strategies should be explored to enhance the production of antiviral peptide drugs, microbicides, and vaccines.