Abstract
Schwartz-Jampel syndrome (SJS) is an autosomal recessive human disorder characterized by myotonia and osteoarticular deformities. Three types are distinguished based on age at onset: types 1A, 1B and 2. We have previously localized the SJS1 gene, responsible for types 1A and 1B, on human chromosome 1p35-p36.1 in a region frequently rearranged in human tumours. The CDC42 gene, for which divergent localizations have previously been described (chromosomes 4, 7 and 20), has been mapped within the SJS1 critical interval by radiation hybrid and yeast/P1 artificial-chromosome-based physical map analyses. The CDC42 gene product is a small GTPase protein of the Rho family mediating a variety of signaling pathways including cytoskeletal rearrangements, cell-cycle progression and transformation. To search for mutations in SJS1 patients, we have determined the organization of the human CDC42 gene on chromosome Ip and found that it encodes for the placental and brain isoforms generated by alternative splicing. No mutations have been found in SJS1 patients, excluding CDC42 as the SJS1 gene. Interestingly, we have demonstrated that a CDC42-like transcript gene located on chromosome 4 does not contain introns and is similar to the placental isoform, suggesting that it is a processed pseudogene. The determination of the CDC42 gene structure described in this report should facilitate future studies of the potential role of CDC42 in human disorders.