Lynch Syndrome Associated with Two MLH1 Promoter Variants and Allelic Imbalance of MLH1 Expression

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Lynch Syndrome Associated with Two MLH1 Promoter Variants and Allelic Imbalance of MLH1 Expression

Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) wit...

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Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome.

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 ...

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Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis.

PURPOSE Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results cannot be used for clinical diagnosis. We therefore aimed to establish a laboratory test that...

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MLH1 Ile219Val Polymorphism in Argentinean Families with Suspected Lynch Syndrome

1 Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway, 2 Unit of Muscle Biology, Lund Transgenic Core Facility/Reproductive Immunology, Department of Experimental Medical Science, Lund University, Lund, Sweden, 3 Institute of Basic Sciences and Experimental Medicine (ICBME), Instituto Universitario Hospital Italiano, Buenos Aires, Argentina, 4 Prog...

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Prediction of MLH1 and MSH2 mutations in Lynch syndrome.

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ژورنال

عنوان ژورنال: Human Mutation

سال: 2015

ISSN: 1059-7794,1098-1004

DOI: 10.1002/humu.22785