+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

An AT-rich region in the adenomatous polyposis coli APC gene may cause misinterpretation of Familial Adenomatous Polyposis molecular screening



An AT-rich region in the adenomatous polyposis coli APC gene may cause misinterpretation of Familial Adenomatous Polyposis molecular screening







Familial adenomatous polyposis (FAP) is an autosomal dominant condition mainly due to a mutation of the adenomatous polyposis coli (APC) gene. The present study reports evidence of a technical issue occurring during the mutational analysis of APC exon 4. Genetic conventional direct sequence analysis of a repetitive AT-rich region in the splice acceptor site of APC intron 3 could be misinterpreted as a pathogenetic frameshift result. However, this potential bias may be bypassed adopting a method for random mutagenesis of DNA based on the use of a triphosphates nucleoside analogues mixture. Using this method as a second level analysis we also demonstrated the non-pathogenic nature of the variant in the poly A trait in APC exon 4 region (c.423-4delA) that do not result in aberrant splicing of APC exons 3-4, conversely we did not find a previously reported T deletion/insertion polymorphism.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036336863

Download citation: RISBibTeXText

DOI: 10.1002/humu.22043


Related references

An AT-rich region in the APC gene may cause misinterpretation of familial adenomatous polyposis molecular screening. Human Mutation 33(5): 895-898, 2012

Screening for mutations of the adenomatous polyposis coli gene in 67 Italian familial adenomatous polyposis Further evidence of complex genotype-phenotype correlations. Gastroenterology 114(4 Part 2): A566, 1998

Germ line mutations of adenomatous of adenomatous polyposis coli apc gene in a series of french propositi for familial adenomatous polyposis. Gastroenterology 102(4 Part 2): A384, 1992

Targeted next-generation sequencing approach for molecular genetic diagnosis of hereditary colorectal cancer: Identification of a novel single nucleotide germline insertion in adenomatous polyposis coli gene causes familial adenomatous polyposis. Molecular Genetics and Genomic Medicine 7(1): E00505, 2019

Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis. Molecular Medicine Reports 18(6): 4931-4939, 2018

Molecular diagnosis of familial adenomatous polyposis (FAP): Genotyping of adenomatous polyposis coli (APC) alleles by MALDI-TOF mass spectrometry. Clinical Biochemistry 35(2): 87-92, 2002

The relationships between phenotypic expression in patients with familial adenomatous polyposis (FAP) and the site of mutations in the adenomatous polyposis coli (APC) gene. Annals of Surgery 229(3): 445-446, 1999

A novel pathogenic large germline deletion in adenomatous polyposis coli gene in a Chinese family with familial adenomatous polyposis. Oncotarget 7(31): 50392-50400, 2016

A novel frameshift mutation in exon 12 of the adenomatous polyposis coli gene in an Italian family with familial adenomatous polyposis and desmoid tumour. Journal of Molecular and Genetic Medicine 4: 235-238, 2010

Cranial desmoid tumor associated with homozygous inactivation of the adenomatous polyposis coli gene in a 2-year-old girl with familial adenomatous polyposis. Cancer. 77(5): 972-976, 1996

Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations. American Journal of Pathology 157(3): 747-754, 2000

Thyroid Carcinoma Usually Occurs in Patients with Familial Adenomatous Polyposis in the Absence of Biallelic Inactivation of the Adenomatous Polyposis Coli Gene. Journal of Clinical Endocrinology & Metabolism 86(1): 427-432, 2001

Analysis of adenomatous polyposis coli gene mutations in familial adenomatous polyposis patients at increased risk for periampullary neoplasia. Proceedings of the American Association for Cancer Research Annual Meeting 34: 517, 1993

Thyroid carcinoma usually occurs in patients with familial adenomatous polyposis in the absence of biallelic inactivation of the adenomatous polyposis coli gene. Journal of Clinical Endocrinology and Metabolism 86(1): 427-432, 2001

Somatic mutations of the adenomatous polyposis coli gene in gastroduodenal tumors from patients with familial adenomatous polyposis. Cancer Research 55(14): 3165-3170, 1995