Abstract
THE Coffin-Lowry syndrome (CLS), an X-linked disorder, is characterized by severe psychomotor retardation, facial and digital dysmorphisms, and progressive skeletal deformations1. Genetic linkage analysis mapped the CLS locus to an interval of 2–3 megabases at Xp22.2. The gene coding for Rsk-2, a member of the growth-factor-regulated protein kinases, maps within the candidate interval, and was tested as a candidate gene for CLS. Initial screening for mutations in the gene for Rsk-2 in 76 unrelated CLS patients revealed one intragenic deletion, a nonsense, two splice site, and two missense mutations. The two missenses affect sites critical for the function of Rsk-2. The mutated Rsk-2 proteins were found to be inactive in a S6 kinase assay. These findings provide direct evidence that abnormalities in the MAPK/RSK signalling pathway cause Coffin-Lowry syndrome.
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Trivier, E., De Cesare, D., Jacquot, S. et al. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature 384, 567–570 (1996). https://doi.org/10.1038/384567a0
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DOI: https://doi.org/10.1038/384567a0
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