Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.
Trivier, Elisabeth; De Cesare, Dario; Jacquot, Sylvie; Pannetier, Solange; Zackai, Elaine; Young, Ian; Mandel, Jean-Louis; Sassone-Corsi, Paolo; Hanauer, Andre
[Letter] Nature. 384(6609):567-570, December 12, 1996.

(Format: HTML)

The Coffin-Lowry syndrome (CLS), an X-linked disorder, is characterized by severe psychomotor retardation, facial and digital dysmorphisms, and progressive skeletal deformations [1]. 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.

(C) 1996 Macmillan Magazines Ltd.