TY - JOUR
T1 - Familial adenomatous polyposis coli
T2 - five novel mutations in exon 15 of the adenomatous polyposis coli (APC) gene in Italian patients. Mutations in brief no. 225. Online.
AU - Scarano, M. I.
AU - De Rosa, M.
AU - Panariello, L.
AU - Carlomagno, N.
AU - Riegler, G.
AU - Rossi, G. B.
AU - Bucci, L.
AU - Pesce, G.
AU - Toni, F.
AU - Renda, A.
AU - Izzo, P.
PY - 1999
Y1 - 1999
N2 - Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain-terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction-single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.
AB - Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain-terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction-single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.
UR - http://www.scopus.com/inward/record.url?scp=0032612934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032612934&partnerID=8YFLogxK
M3 - Article
C2 - 10090483
AN - SCOPUS:0032612934
VL - 13
SP - 256
EP - 257
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 3
ER -