Implication of adenomatous polyposis coli and MUTYH mutations in familial colorectal polyposis.
OBJECTIVE
Familial adenomatous polyposis is an autosomal dominantly inherited syndrome characterized by hundreds or thousands of colorectal polyps and a high risk of colorectal cancer at a young age. Truncating germline mutations in the adenomatous polyposis coli gene are detected in approximately 80 percent of patients with classical familial adenomatous polyposis and in approximately 10 percent of the attenuated familial adenomatous polyposis patients.


METHODS
We investigated the adenomatous polyposis coli and MUTYH genes mutations in a well-characterized series of 25 unrelated Italian patients with familial adenomatous polyposis.


RESULTS
We characterized the specific adenomatous polyposis coli gene mutation in 10 probands, and identified eight truncating mutations (4 novel and 4 known mutations) and two splicing mutations. One of these, a novel missense mutation in exon 15, activates an exonic splicing enhancer control sequence. Moreover, 11 MUTYH gene mutations have been identified in 7 patients without a dominant family history of polyposis.


CONCLUSIONS
This study enlarges the genotype-phenotype correlations of familial adenomatous polyposis and suggests that messenger alterations could be responsible for a subset of familial adenomatous polyposis cases without germ-line adenomatous polyposis coli or MUTYH gene mutations. It also confirms that genotype-phenotype correlations in MUTYH-associated polyposis are very complex.
De Rosa
Marina
M
Dipartimento di Biochimica e Biotecnologie Mediche and CEINGE Biotecnologie Avanzate, Università di Napoli Federico II, Napoli, Italy.
Galatola
Martina
M
Borriello
Santa
S
Duraturo
Francesca
F
Masone
Stefania
S
Izzo
Paola
P
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D045647:DNA Glycosylases / Q000235:genetics*; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase