Premium
Exon eight APC mutations account for a disproportionate number of familial adenomatous polyposis families
Author(s) -
Koorey David J.,
McCaughan Geoffrey W.,
Trent Ronald J.,
Gallagher Neil D.
Publication year - 1994
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380030103
Subject(s) - exon , familial adenomatous polyposis , genetics , frameshift mutation , biology , adenomatous polyposis coli , point mutation , gene , mutation , stop codon , coding region , colorectal cancer , cancer
The familial adenomatous polyposis gene, APC , has recently been identified. Detection of APC mutations will facilitate genetic screening in family members at risk for this disease. The length of APC makes it impractical to examine the entire coding sequence in each new family encountered. Identification of mutation cluster regions within the gene has therefore become a priority. Initial reports suggested that exon eight might contain a disproportionate number of mutations. This study describes direct sequencing of exon eight in 21 unrelated Australians with familial adenomatous polyposis. Mutations were detected in three of the 21 subjects (14%). Two were previously described point mutations changing an arginine to a stop codon. The third was a novel two base‐pair deletion producing a frameshift and downstream stop codon. All three mutations segregated with the disease gene in their respective families. Three at risk children from two of these families were studied and shown not to have inherited the disease producing mutation. These results confirm that exon eight is a frequent site of mutation in familial adenomatous polyposis and should be examined routinely in families requesting genetic screening. © 1994 Wiley‐Liss, Inc.