title: Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations.
abstract: 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.
authors.affiliation: Unité de Recherches, INSERM U-393, Hôpital des Enfants-Malades, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Bénit
authors.forename: A
authors.initials: A
authors.lastname: Kara-Mostefa
authors.forename: S
authors.initials: S
authors.lastname: Hadj-Rabia
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J P
authors.initials: JP
authors.lastname: Bonnefont
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D011506:Proteins; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins