NOVEL MUTATIONS IN THE APC GENE AND CLINICAL-FEATURES IN SWEDISH PATIENTS WITH POLYPOSIS-COLI

The adenomatous polyposis coli (APC) gene was investigated in Swedish patients with familial adenomatous polyposis (FAP). A combination of a nalyses including single stranded conformation polymorphism (SSCP), he teroduplex (HD), protein truncation test (PTT) and direct sequencing w as used to enable optimal mutation detection. Three novel mutations in the gene were identified, i.e. nt2644C->T (giving an Arg876Stop mutat ion), nt4025del173 (leading to premature truncation of the protein at codon 1337) and nt3526insG (giving truncation at codon 1178). In addit ion, one previously described mutation, i.e. the 5-bp-deletion nt3942d e15(AAAGA) in codon 1309 (giving a premature termination of the protei n at codon 1314) was detected All four mutations were located in the 5 '-half of exon 15. The two latter mutations were associated with the C HRPE (congenital hypertrophy of retina pigment epithelium) phenotype ( CHRPE was not examined in the other two cases). The patients with muta tions in codon 1309 and 1336 had a more severe FAP phenotype.