Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations

Considering the prevalence of truncating mutations in the tuberous sclerosi s (TSC) hamartin gene (TSC1), we devised a protein truncation rest (PTT) to analyze the full length coding sequence of TSC1, Studying 12 sporadic case s and three familial forms by a combination of MT and single-strand conform ation polymorphism analysis (SSCA), we found 5/15 mutations while PTT alone detected 4/15 truncating mutations, two of which escaped SSCA analysis. SS CA alone picked up one missense mutation and two mutations also detected by PTT. Interestingly, a TSC1 mutation was identified in all three familial f orms (3/3) while the rate of mutation detection was lower in sporadic cases (2/12). Zn conclusion, PTT proves to be a useful technique for the rapid d etection of disease-causing mutations in the TSC1 gene. Hum Mutat 14:428-43 2, 1999. (C) 1999 Wiley Liss, Inc.