IDENTIFICATION AND CHARACTERIZATION OF THE TUBEROUS SCLEROSIS GENE ONCHROMOSOME-16

Tuberous sclerosis (TSC) is an autosomal dominant multisystem disorder with loci assigned to chromosomes 9 and 16. Using pulsed-field gel el ectrophoresis (PFGE), we identified five TSC-associated deletions at 1 6p13.3. These were mapped to a 120 kb region that was cloned in cosmid s and from which four genes were isolated. One gene, designated TSC2, was interrupted by all five PFGE deletions, and closer examination rev ealed several intragenic mutations, including one de novo deletion. In this case, Northern blot analysis identified a shortened transcript, while reduced expression was observed in another TSC family, confirmin g TSC2 as the chromosome 16 TSC gene. The 5.5 kb TSC2 transcript is wi dely expressed, and its protein product, tuberin, has a region of homo logy to the GTPase-activating protein GAP3.