The document summarizes the laboratory diagnosis of tuberous sclerosis through genetic testing. It discusses two genes, TSC1 and TSC2, that are associated with the disease. Mutation detection methods including multiplex ligation-dependent probe amplification and DNA sequencing are able to identify mutations in approximately 75% of cases. The summary also notes that comprehensive genetic testing still fails to find mutations in all patients.

1. The Laboratory Diagnosis of Tuberous Sclerosis Michael Buckley FHGSA FRCPA PhD Director, SEALS Genetics Laboratories Prince of Wales & Sydney Children’s Hospitals SEALS Genetics

2. Advances in Tuberous Sclerosis: From Pathway to Therapy Medical and Family Conference 3 – 4 November 2007 Sydney Children’s Hospital Randwick For more information: www.atss.org.au

4. 2. Sensitivity of Mutation Detection SEALS Genetics Overall, there is a mutation detection sensitivity of approximately 75% MLPA on Previously Screened Mutation Negative Samples Mutation Screening Results for Small Mutations in TSC

5. 3. Mutation Types SEALS Genetics GeneTests website

8. 7. TSC MLPA results SEALS Genetics Three MLPA identified mutations in a cohort of 50 patients Contrary to published data the NSW TSC2 deletion frequency is lower than that of TSC1

9. 8. TSC mutation screen results SEALS Genetics

11. 9. Where are the missing mutations? SEALS Genetics

12. 10. TSC1 Evolutionary conservation SEALS Genetics

13. 11. TSC2 Evolutionary conservation SEALS Genetics

15. Advances in Tuberous Sclerosis: From Pathway to Therapy Medical and Family Conference 3 – 4 November 2007 Sydney Children’s Hospital Randwick For more information: www.atss.org.au