Application of the Protein Truncation Test (PTT) for the Detection of Tuberosis Sclerosis Complex Type 1 and 2 (TSC1 andTSC2) Mutations

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of widespread hamartomas affecting most organs including the brain, heart, skin, kidney, lung, and eyes. Involvement of the brain is associated with some of the most severe clinical problems of TSC, including epilepsy, intellectual disability, and abnormal behavioral phenotypes. Inactivating mutations have been identified in two disease-causing genes, TSC1 on chromosome 9q34 (MIM *191100) (1 ) and TSC2 on chromosome 16p13 (MIM * 191092) (2 ). TSC affects up to 1 in 6000 individuals with two-thirds representing sporadic cases, reflecting a high spontaneous mutation rate. Both TSC genes cover about 50 kb and 40 kb of genomic DNA, respectively. The TSC1 gene contains 23 exons with 21 exons coding for a 8.6 kb transcript which is translated into the protein hamartin. The TSC2 gene product tuberin is encoded by an mRNA of 5.5 kb consisting of 41 exons.