Analysis of germline mutations in the APC gene in familial adenomatous polyposis patients.
OBJECTIVE
This study was aimed at establishing an efficient mutation analysis technique system to screen the germline mutations in the adenomatous polyposis coli (APC) gene that predisposes the disease susceptibility in familial adenomatous polyposis (FAP) and to investigate the relationship between genotype and phenotype of APC gene.


METHODS
Genomic DNA was extracted from the peripheral blood lymphocytes of 22 patients with clinically diagnosed FAP and was forwarded to screening for germline mutations by using denaturing high-performance liquid chromatography(DHPLC), protein truncation test (PTT) and DNA sequencing in APC gene. Analysis of genotype-phenotype was also performed on the clinical data of the FAP patients.


RESULTS
Thirteen APC germline mutations were identified in 22 FAP patients. All of the mutations were nonsense or framshift mutations. Analysis of genotype-phenotype demonstrated that the FAP patients with mutations in the 5'or 3'extreme parts of the APC gene showed mild clinical symptoms. However, the FAP patients with mutations in the middle of the APC gene displayed typical or severe clinical symptoms.


CONCLUSIONS
The technique system established in this study can efficiently and sensitively detect the mutations in APC gene. It is useful in the molecular diagnosis of pre-symptomatic FAP cases in FAP family. The clinical features of FAP patients may be related to their genotypes of APC gene.
Liu
Xiao-rong
XR
Department of Medical Genetics, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, PR China.
Shan
Xiang-nian
XN
Friedl
W
W
Uhlhaas
S
S
Propping
P
P
Wang
Ya-ping
YP
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation / Q000235:genetics; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D010641:Phenotype; D016133:Polymerase Chain Reaction
D025601:Adenomatous Polyposis Coli Protein