First genotype characterization of Argentinean FAP patients: identification of 14 novel APC mutations.
We examined the adenomatous polyposis coli (APC) gene for disease-causing mutations in 51 unrelated Argentinean probands affected by familial adenomatous polyposis (FAP). Using a combination of the protein truncation test, the single strand conformation polymorphism technique, DNA sequencing and quantitative PCR analysis, we identified the specific mutation in 39 (average age: 28.4 years) of the 51 probands (detection rate: 76.47%); 13 are novel germline mutations and one is a novel sequence variant. There were 27 small deletions, four small duplications, five nonsense mutations in exon 15, three nonsense mutations in exons 6, 11, and 12, and one sequence variant in exon 3 identified in a patient bearing a truncating mutation in exon 15. The most common mutation (found in 10 cases) was at codon 1309. All patients negative for APC mutations were also negative for the MutY homolog (MYH) gene mutation, as expected because of fully penetrant FAP cases. This study enlarges the spectrum of APC gene mutations, and reinforces the concept of mutation heterogeneity. It also sheds light on correlations between the site of APC germline mutations and the clinical manifestations of FAP. Our data indicate that the genotype/phenotype correlations in Argentinean patients are similar to those observed in other populations.
De Rosa
Marina
M
Dipartimento di Biochimica e Biotecnologie Mediche, Unversità di Napoli Federico II, Naples, Italy.
Dourisboure
Ricardo J
RJ
Morelli
Gemma
G
Graziano
Alfredo
A
Gutiérrez
Alejandro
A
Thibodeau
Stephen
S
Halling
Kevin
K
Avila
Karina Collia
KC
Duraturo
Francesca
F
Podesta
Ernesto J
EJ
Izzo
Paola
P
Solano
Angela R
AR
D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001118:Argentina; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017491:Genes, APC; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation