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A Novel Exon Duplication Event Leading to a Truncating Germ-line Mutation of the APC Gene in a Familial Adenomatous Polyposis Family

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Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition predisposing to multiple adenomatous polyps of the colon. FAP patients frequently carry heterozygous mutations of the APC tumour suppressor gene. Affected individuals from a cohort of FAP families (n=22), where no germ-line APC mutation was detected by direct sequencing, were analysed by Multiplex Ligation-dependent Probe Amplification (MLPA). MLPA identified a previously unreported APC mutation involving duplication of exon 4. Subsequent analysis of cDNA from affected family members revealed expression of mutant mRNA species containing two copies of exon 4, resulting in a frameshift and premature stop codon. Bioinformatic analysis of the relevant APC genomic segment predicted a role for homologous recombination possibly involving Alu repeats in the generation of this genotype. Our results highlight the importance of MLPA as an adjunct to exon-by-exon sequencing in identifying infrequent mutational events in cancer predisposing genes.

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Adenomatous Polyposis Coli


Congenital Hypertrophy of the Retinal Pigment Epithelium


Familial Adenomatous Polyposis


Multiplex Ligation-dependent Probe Amplification


Protein Truncation Test


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Correspondence to Andrew Silver.

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Amy McCart and Andrew Latchford contributed equally to this work.

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McCart, A., Latchford, A., Volikos, E. et al. A Novel Exon Duplication Event Leading to a Truncating Germ-line Mutation of the APC Gene in a Familial Adenomatous Polyposis Family. Familial Cancer 5, 205–208 (2006).

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