ABSTRACT
BACKGROUND: A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. METHODS: Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. RESULTS AND CONCLUSION: A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fusion transcripts between MLH1 and LRRFIP2. A single-nucleotide polymorphism in MLH1 exon 8 was expressed from both alleles, initially pointing to appropriate MLH1 function at least in peripheral cells. In a second case, an inherited duplication of the MLH1 gene region resulted in constitutional MLH1 promoter methylation. Constitutional MLH1 promoter methylation may therefore in rare cases be a heritable disease mechanism and should not be overlooked in seemingly sporadic patients.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Methylation/genetics , DNA, Complementary/genetics , Gene Rearrangement/genetics , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic , Alleles , Base Sequence , Chromosome Inversion/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , DNA Mutational Analysis , Exons/genetics , Family , Female , Gene Duplication/genetics , Genetic Testing , Genome, Human/genetics , Humans , Male , Molecular Sequence Data , MutL Protein Homolog 1 , PedigreeABSTRACT
We investigated whether a novel monoclonal stool antigen test for detection of Helicobacter pylori performs with the same accuracy as the (13)C-urea breath test (UBT) for adult outpatients in the setting of a private office. The two tests showed identical levels of sensitivity when used to identify H. pylori-infected patients before and after eradication therapy.