Bénit P, Kara-Mostefa A, Hadj-Rabia S, Munnich A, Bonnefont J P
Unité de Recherches, INSERM U-393, Hôpital des Enfants-Malades, Paris, France.
Hum Mutat. 1999;14(5):428-32. doi: 10.1002/(SICI)1098-1004(199911)14:5<428::AID-HUMU9>3.0.CO;2-5.
Considering the prevalence of truncating mutations in the tuberous sclerosis (TSC) hamartin gene (TSC1), we devised a protein truncation test (PTT) to analyze the full length coding sequence of TSC1. Studying 12 sporadic cases and three familial forms by a combination of PTT and single-strand conformation polymorphism analysis (SSCA), we found 5/15 mutations while PTT alone detected 4/15 truncating mutations, two of which escaped SSCA analysis. SSCA alone picked up one missense mutation and two mutations also detected by PTT. Interestingly, a TSC1 mutation was identified in all three familial forms (3/3) while the rate of mutation detection was lower in sporadic cases (2/12). In conclusion, PTT proves to be a useful technique for the rapid detection of disease-causing mutations in the TSC1 gene.
