Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
MOLECULAR ANALYSIS OF THE APC GENE IN 105 DUTCH KINDREDS WITH FAMILIAL ADENOMATOUS POLYPOSIS - 67 GERMLINE MUTATIONS IDENTIFIED BY DGGE, PTT, AND SOUTHERN ANALYSIS
Autore:
VANDERLUIJT RB; KHAN PM; VASEN HFA; TOPS CMJ; VANLEEUWENCORNELISSE ISJ; WIJNEN JT; VANDERKLIFT HM; PLUG RJ; GRIFFIOEN G; FODDE R;
Indirizzi:
LEIDEN UNIV,FAC MED,SYLVIUS LABS,MED GENET CTR,MGC,DEPT HUMAN GENET LEIDEN NETHERLANDS LEIDEN UNIV,CTR MED,MEDIPARK,NETHERLANDS FDN DETECT HEREDITARY TUMORSNL-2300 RA LEIDEN NETHERLANDS LEIDEN UNIV,DEPT GASTROENTEROL LEIDEN NETHERLANDS
Titolo Testata:
Human mutation
fascicolo: 1, volume: 9, anno: 1997,
pagine: 7 - 16
SICI:
1059-7794(1997)9:1<7:MAOTAG>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
GRADIENT-GEL-ELECTROPHORESIS; COLI GENE; LINE MUTATIONS; RAPID DETECTION; CHROMOSOME-5Q21; REGION; FAP; DIAGNOSIS; EXONS;
Keywords:
APC GENE; FAMILIAL ADENOMATOUS POLYPOSIS; GERMLINE MUTATIONS; PRESYMPTOMATIC DIAGNOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
R.B. Vanderluijt et al., "MOLECULAR ANALYSIS OF THE APC GENE IN 105 DUTCH KINDREDS WITH FAMILIAL ADENOMATOUS POLYPOSIS - 67 GERMLINE MUTATIONS IDENTIFIED BY DGGE, PTT, AND SOUTHERN ANALYSIS", Human mutation, 9(1), 1997, pp. 7-16

Abstract

Germline mutations of the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to colorectal cancer. We screened the entire coding region of the APC gene for mutations in an unselected series of 105 Dutch FAP kindreds. For the analysis of exons 1-14, we employed the GCclamped denaturing gradient gel electrophoresis (DGGE), while the large exon 15 was examined using the protein truncation test. Using this approach, we identified 65 pathogenic mutations in the above 105 apparently unrelated FAP families. The mutations were predominantly either frameshifts (39/65) or single base substitutions (18/65), resulting inpremature stop codons. Mutations that would predict abnormal RNA splicing were identified in seven cases. In one of the families, a nonconservative amino acid change was found to segregate with the disease. Inspite of the large number of APC mutations reported to date, we identified 21 novel germline mutations in our patients, which reiterates the great heterogeneity of the mutation spectrum in FAP. In addition to the point mutations identified in our patients, structural rearrangements of APC were found in two pedigrees, by Southern blot analysis. Thepresent study indicates that the combined use of DGGE, protein truncation test, and Southern blot analysis offers an efficient strategy forthe presymptomatic diagnosis of FAP by direct mutation detection. We found that the combined use of the currently available molecular approaches still fails to identify the underlying genetic defect in a significant subset of the FAP families. The possible causes for this limitation are discussed. (C) 1991 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 19:01:57