Gm. Petersen et al., PRESYMPTOMATIC DIRECT-DETECTION OF ADENOMATOUS POLYPOSIS-COLI (APC) GENE-MUTATIONS IN FAMILIAL ADENOMATOUS POLYPOSIS, Human genetics, 91(4), 1993, pp. 307-311
The recent identification of the familial adenomatous polyposis (FAP)
gene (designated as APC) enables conclusive genetic testing of at-risk
family members for the specific mutation in families in which the ger
mline gene mutation has been characterized. Presymptomatic molecular d
iagnosis of FAP was performed by direct direction of mutations in lymp
hocyte DNA in four families. Each of the families has a different muta
tion of the APC gene. Twenty-seven offspring of affected individuals (
a priori risk of 50%) were tested. Ten of the 27 had already developed
clinical features of FAP. Of the remaining seventeen, two had had a n
egative colon exam at an early age, and nine had never had colon exams
(mean age, 12.1 +/- 3.1 SD years). Six children from this group (54%)
were found to carry their affected parent's mutation. No change in th
e conventional FAP colon screening regimen is recommended for these ch
ildren. In contrast, when direct tests indicate that an individual doe
s not have the FAP mutation, we recommended that screening be decrease
d. Reduction of uncertainty for at-risk FAP family members is an impor
tant benefit of genetic testing.