Coffin-Lowry syndrome (CLS) is an X-linked disorder characterized by growth and psychomotor retardation, hypotonia and progressive skeletal changes. RPS6KA3 is the only gene known to be associated with CLS, and over 150 distinct inactivating mutations in this gene have so far been reported in CLS patients. However, no defect is found in about half of the CLS compatible patients by exon sequencing. We report here the first deep intronic mutation in RPS6KA3, which is associated with the retention of intronic sequences in the mRNAs. Indeed, this finding suggests that all the patients with a highly suggestive CLS clinical diagnosis, but in whom exon screening has failed to detect a mutation, should be reanalyzed at the RNA level.
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