Genetic testing for TSC
Since the identification of the TSC1 and TSC2 genes, thousands of individuals have had disease-causing mutations identified. Roughly three quarters of the tested individuals had mutations in the TSC2 gene, while the remaining quarter had mutations in TSC1.
Genetic testing of both genes is complicated by the large size of the two genes, the large number of disease-causing mutations and the high rate of somatic mosaicism (which means that some cells carry the mutations, but other cells may not).
Mutations of the TSC1 gene are usually small deletions, insertions and nonsense mutations that can be detected by a complex DNA sequencing test for combined tuberous sclerosis. TSC2 mutations include significant numbers of large deletions and rearrangements that can not be detected by sequence analysis. Several studies that aimed to identify the disease-causing mutation through sequence analysis, were able to do so in 70-80% of the cases.
- Deletion/duplication analysis
The most sensitive method to identify large gene deletions is multiple ligation-dependent probe amplification (MLPA). MLPA is a variation of the polymerase chain reaction that permits multiple targets to be amplified with only a single primer pair. Using this method, scientists have been able to identify large or whole-gene mutations in over a quarter of the families in which no mutation had been identified by sequence analysis.