engleski

Genetic analysis of the APC gene in the diagnostics of familial adenomatous polyposis

BACKGROUND: The purpose of this study was to determine the usefulness of a APC gene mutation detection in presymptomatic diagnostics of FAP and to show importance of genetic analysis in differentiation of polyposis syndromes and confirmation of FAP diagnosis. FAP patients develop hundreds to thousands of adenomatous polyps in the colon and one or more of them progress to cancer if left without surgical treatment. Because FAP patients have a very high risk of colorectal cancer, identification of the individual risk in family members is important to prevent cancer deaths. The method of providing such accurate presymptomatic diagnosis is to determine whether a family member has inherited the germ-line mutation of the APC gene. The most frequent germ-line mutations were found to occur at codons 1307-1311. The frequency of this mutation reaches 24% of the total mutations detected. MATERIAL AND METHOD: DNAs were isolated from peripheral blood of patients and their relatives. PCR products were analyzed by electrophoresis on a Spredex EL 300 gels. RESULT: After only 110 min PCR fragments of 91 and 86 bp (5 bp deletion in codon 1309) were completely resolved on a Spredex EL 300 gel. Results showed that the mutation in codon 1309 is the most common germ-line mutation in FAP families in Croatia. CONCLUSIONS: Electrophoresis using Spredex gels provides a simple and rapid method for determination of the most frequent germ-line mutations in the APC gene. We use this method in presymptomatic diagnosis but also to confirm the diagnosis of FAP in the differential diagnostics of the polyposis syndromes.

APC; FAP; germline mutations

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