BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary colon cancer syndrome accounting for 1-5% of all colorectal cancer cases. Germline mutations in DNA mismatch repair (MMR) genes are associated with the clinical phenotype of HNPCC. Defects in the MSH2 gene may account for about 40% of HNPCC cases including nucleotide substitutions, deletions and insertions. Only a few mutations were reported in Chinese families. This study was performed to identify the disease-causing gene mutation(s) and conduct pre-symptomatic diagnosis in a Chinese family with HNPCC. MATERIALS AND METHODS: Mutation analysis in MLH1 and MSH2 followed by pre-symptomatic diagnosis in MSH2 was performed on genomic DNA isolated from the family members. RESULTS: A novel duplication mutation of four nucleotides in exon 7 of MSH2 (MSH2: c.1216_1219dupCGAC) resulting in a premature stop 10 codons downstream in MSH2 (p.L407fsX417) was found. The mutation was associated with HNPCC and an asymptomatic carrier was found in the family. CONCLUSION: HNPCC in a Chinese family is associated with a novel mutation in the MSH2 gene (MSH2: c.1216_1219dupCGAC).
BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary colon cancer syndrome accounting for 1-5% of all colorectal cancer cases. Germline mutations in DNA mismatch repair (MMR) genes are associated with the clinical phenotype of HNPCC. Defects in the MSH2 gene may account for about 40% of HNPCC cases including nucleotide substitutions, deletions and insertions. Only a few mutations were reported in Chinese families. This study was performed to identify the disease-causing gene mutation(s) and conduct pre-symptomatic diagnosis in a Chinese family with HNPCC. MATERIALS AND METHODS: Mutation analysis in MLH1 and MSH2 followed by pre-symptomatic diagnosis in MSH2 was performed on genomic DNA isolated from the family members. RESULTS: A novel duplication mutation of four nucleotides in exon 7 of MSH2 (MSH2: c.1216_1219dupCGAC) resulting in a premature stop 10 codons downstream in MSH2 (p.L407fsX417) was found. The mutation was associated with HNPCC and an asymptomatic carrier was found in the family. CONCLUSION: HNPCC in a Chinese family is associated with a novel mutation in the MSH2 gene (MSH2: c.1216_1219dupCGAC).
Authors: M Miyaki; M Konishi; K Tanaka; R Kikuchi-Yanoshita; M Muraoka; M Yasuno; T Igari; M Koike; M Chiba; T Mori Journal: Nat Genet Date: 1997-11 Impact factor: 38.330
Authors: L A Aaltonen; P Peltomäki; F S Leach; P Sistonen; L Pylkkänen; J P Mecklin; H Järvinen; S M Powell; J Jen; S R Hamilton Journal: Science Date: 1993-05-07 Impact factor: 47.728
Authors: F S Leach; N C Nicolaides; N Papadopoulos; B Liu; J Jen; R Parsons; P Peltomäki; P Sistonen; L A Aaltonen; M Nyström-Lahti Journal: Cell Date: 1993-12-17 Impact factor: 41.582
Authors: N C Nicolaides; N Papadopoulos; B Liu; Y F Wei; K C Carter; S M Ruben; C A Rosen; W A Haseltine; R D Fleischmann; C M Fraser Journal: Nature Date: 1994-09-01 Impact factor: 49.962