Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant multi-system disorder with two known disease loci on chromosomes 9q34 (TSC1) and 16p13.3 (TSC2). TSC has a prevalence of approximately 1 in 5,000-6,000, exhibits incomplete penetrance, and occurs in all racial groups. Our laboratory has undertaken the complete mutation analysis of the TSC2 gene in 42 TSC families using single-strand conformation polymorphism analysis and reverse transcription-polymerase chain reaction. Of the total of 42 families, 16 show evidence of linkage to the chromosome 16 TSC2 locus and 26 are either sporadic or too small to establish chromosome linkage. The TSC2 gene spans at least 45 kilobases of genomic DNA, has 41 known exons, and codes for a 5,474-base pair transcript. After complete gene analysis, 16 TSC2 mutations have been identified, including DNA insertions, deletions, splice site mutations, and amino acid substitutions. The majority of putative TSC2 mutations were found in sporadic rather than TSC2-linked families. We have also detected 15 polymorphisms which occur in the TSC2 gene.