LETTER TO JMG

A novel aberrant splice site mutation in the APC gene

G S Charames^1,2,4, H Cheng¹, C A Gilpin⁵, A G W Hunter⁵, T Berk³, B Bapat^1,2,3,4

¹ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada
² Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
³ Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Canada
⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
⁵ Eastern Ontario Regional Genetics Program, Children’s Hospital of Eastern Ontario, Ottawa, Canada

Correspondence to:
Correspondence to:
Dr B Bapat, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Room 992B, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5;
bapat@mshri.on.ca

Keywords: APC gene; familial adenomatous polyposis; aberrant splicing; cryptic splice acceptor site

Abbreviations: FAP, familial adenomatous polyposis; CRC, colorectal cancer; CHRPE, congenital hypertrophy of the retinal pigment epithelium; APC, adenomatous polyposis coli; SD, splice donor; SA, splice acceptor; PTT, protein truncation test; AAPC, attenuated APC

The first 150 words of the full text of this article appear below.

Familial adenomatous polyposis (FAP) is an inherited, autosomal dominant syndrome characterised by the presence of multiple (>100) adenomatous polyps in the colon and rectum. These polyps, if left untreated, progress to colorectal cancer (CRC), typically by the age of 40 years.¹ Other clinical features include variable age of onset of polyposis (age 10-40 years) and variable expression.² FAP accounts for about 1% of all colorectal cancers.^3,4 In addition to colonic polyps, FAP patients may present premalignant lesions in the upper gastrointestinal tract, extraintestinal manifestations such as osteomas and epidermoid cysts, desmoid formation, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and other malignant changes, such as small bowel cancer and tumours of the brain and thyroid gland.²

FAP is caused by the dominant inheritance of germline mutations of the adenomatous polyposis coli (APC, MIM 175100) tumour suppressor gene.^3–6 APC is a 312 kDa protein translated from a major transcript consisting . . . [Full text of this article]

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