Premium
Protein truncation test for screening hamartin gene mutations and report of new disease‐causing mutations
Author(s) -
Bénit Paule,
KaraMostefa Ali,
HadjRabia Smail,
Munnich Arnold,
Bonnefont JeanPaul
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(199911)14:5<428::aid-humu9>3.0.co;2-5
Subject(s) - tsc1 , biology , genetics , missense mutation , mutation , gene , tsc2 , coding region , mutation testing , gene mutation , apoptosis , pi3k/akt/mtor pathway
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. Hum Mutat 14:428–432, 1999. © 1999 Wiley‐Liss, Inc.