Molecular genetic evidence for the delineation of a more severe form of familial adenomatous polyposis which results from fresh mutation.
Familial adenomatous polyposis, an inherited pre-malignant condition, is caused by mutation in the adenomatous polyposis coli (APC) gene at chromosome 5q22. The lifetime risk of carcinoma approaches 100%, with an average age at death from cancer of 40 years, allowing most patients to complete reproduction. Since there is no evidence for a rising incidence, this is at variance with an apparently high mutation rate. We present evidence for the delineation of a severe form, which hitherto has largely been maintained by fresh mutation. An atypically high frequency of loss of heterozygosity at chromosome 5q22 in small adenomas correlated with an early age of onset or malignancy in two patients, both due to fresh mutation. In both cases, the mutation in APC was shown to be a commonly occurring deletion, leading us to postulate the co-existence of a modifying gene.
Galton Laboratory, Department of Genetics and Biometry, University College London, UK.
M
M
Rees
S E
SE
Leigh
J D
JD
Delhanty
L
L
Bowles
I C
IC
Talbot
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D004252:DNA Mutational Analysis; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation