Clinical findings in a family with familial adenomatous polyposis and a missense mutation of the adenomatous polyposis coli gene.
BACKGROUND
More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function.


METHODS
In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band.


RESULTS
A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects.


CONCLUSIONS
In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.
Analysis Laboratory, Mauriziano Hospital Umberto I, Turin, Italy.
C A
CA
Marchese
F
F
Bertolino
B
B
Ceccopieri
M
M
Vanzetti
D
D
Scaglione
L
L
Locatelli
M
M
Montera
L
L
Romio
N
N
Resta
A
A
Stella
G
G
Guanti
C
C
Mareni
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein; D000328:Adult; D003106:Colon / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000473:pathology; D014364:Tryptophan / Q000235:genetics
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D014364:Tryptophan