UC Irvine

We have identified the presence of chromosomal rearrangements in the 9q34.3 region in two Tuberous sclerosis (TSC) families. We previously reported the use of fluorescence in situ hybridization to identify the presence of a chromosome 9q34.3 duplication in a sporadic case of TSC. We have now defined a chromosomal breakpoint flanking th~ duplication through pulsed field gel electrophoresis (~FGE) . We have also utilized PFGE to define the ~hromosomal rearrangement present in a second TSC family, (TS 33). In TS family 33 we demonstrated the presence of a novel Clar fragment with probes D9Sl0 and DBH, indicating that the TSCl gene mapped within 240kb of DBH and D9Sl0. We previously reported that the D9Sl0 locus contains a gene homologous to the Vav oncogene (Smith et al. , Ann Hurn. Genet. 58: 235-236 1994). In normal individuals, D9Sl0 and DBH. map to the same ClaI fragment. SacII sites lie within this ClaI fragment so that DBH and the D9S122 locus map to a 120kb SacII fragment while D9Sl0 maps to a lOOkb SacII fragments. Using a unique sequence probe which maps adjacent to the telomeric end of the 095122 locus,· we detected a novel fragment in the sporadic case of TSC described above. This finding indicates that the TSCl gene maps within 120kb of the D9Sl22 locus. These rearrangements have facilitated fine mapping of the TSCl locus and their availability will facilitate identificatior:i of the TSCl gene.