APC transcription studies and molecular diagnosis of familial adenomatous polyposis

Emma Short*, Laura E. Thomas, Alice Davies, Alice Bolton, Julie Maynard, Peter Giles, Matthew Mort, Claudia Consoli, Iris Egner, Hala Jundi, Julian R. Sampson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic variants in the APC gene. Index patients with suspected FAP are usually investigated by APC coding region sequence and dosage analysis in a clinical diagnostic setting. The identification of an APC variant which is predicted to alter protein function enables predictive genetic testing to guide the management of family members. This report describes a 4-generation family with a phenotype consistent with FAP, but in which an APC variant had not been identified, despite testing. To explore this further, quantitative PCR (qPCR) was employed to assess APC transcription, demonstrating reduced levels of APC RNA. Next generation sequencing (NGS) identified the APC 5′UTR/ Exon 1 variant, c.-190 G>A, that had been reported previously in an another FAP family with APC allelic imbalance. Quantitative RNA studies and DNA sequencing of the APC promoters/ Exon 1 may be useful diagnostically for patients with suspected FAP when coding region variants cannot be identified.

Original languageEnglish
Pages (from-to)118-121
Number of pages4
JournalEuropean Journal of Human Genetics
Volume28
Issue number1
DOIs
Publication statusPublished - 5 Aug 2019
Externally publishedYes

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