Frameshift Mutations (Deletion at Codon 1309 and Codon 849) in the APC Gene in Iranian FAP Patients: a Case Series and Review of the Literature

Document Type : Original Article

Authors
Seyed Mohammad Hossein Kashfi 1
Faeghe Behboudi Farahbakhsh 2
Mina Golmohammadi 2
Ehsan Nazemalhosseini Mojarad 1
Pedram Azimzadeh 1
1 Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Familial adenomatous polyposis (FAP) is responsible for <1% of colorectal cancer (CRC) cases and is inherited
an autosomal dominant trait. Patients generally present hundreds to thousands of adenomas and develop
colorectal cancer by age 35- 40 if left untreated. Here we report four patients with germline frameshift mutation
(small deletion) at exon 15 of adenomatous polyposis coli (APC) tumor suppressor gene. Peripheral blood
samples were collected from patients and Exon 15 of the APC gene was studied by direct sequencing after
genomic DNA extraction. Four frameshift mutations were detected. Two patients had 5 bp deletion,
c.3927_3931delAAAGA and two siblings presented deletion at codon 849 (c.2547_2548delTA p.Asp849fsX62).
This study was the first report of genetic screening in Iranian FAP patients. In contrast to other studies we
revealed that one patient with mutation at codon 1309 had an attenuated phenotype.
Keywords
Adenomatous polyposis coli
colorectal cancer
frameshift mutation