Functional analysis helps to clarify the clinical importance of unclassified variants in DNA mismatch repair genes. Human Mutation, 2007. Niels Wind. Robert Hofstra. Renée Niessen. Jan Kleibeuker.
Aberrant splicing in MLH1 and MSH2 due to exonic and Dec 08, 2005 · In order to use the variants for predictive testing in persons at risk, their pathogenicity has to be evaluated. There is growing evidence that some substitutions have a detrimental influence on splicing. We examined 19 unclassified variants (UVs) detected in MSH2 or MLH1 genes in patients suspected of HNPCC for eion at RNA level.
May 01, 2013 · We found three missense variants in the MSH2 gene:c.2651T>G (p.I884S), c.2634G>A (p.E878D), and c.1661G>A (p.S554T). The families carrying these variants met the Amsterdam criteria; the tumor phenotype was unstable (MSI) and had deficient eion of the MSH2MSH6 heterodimer.
Evaluating the Effect of Unclassified Variants Identified integrative analysis of UVs; of 23 initially unclassi ed MLH1 or MSH2 missense variants,they classied 11as benign and2 as pathogenic. Kansikas et al20 recently proposed a three-step assessment model. Nonetheless, classication of some of these described substitutions indicates conict between the
Functional Analysis in Mouse Embryonic Stem Cells Reveals Sep 10, 2013 · We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions.
The functional characterization of nonsynonymous single nucleotide polymorphisms in human mismatch repair (MMR) genes has been critical to evaluate their pathogenicity for hereditary nonpolyposis colorectal cancer. We previously established an assay for detecting loss-of-function mutations in the MLH1 gene using a dominant mutator effect of human MLH1 eed in Saccharomyces cerevisiae .
Functional analysis helps to clarify the clinical Oct 11, 2007 · Functional analysis helps to clarify the clinical importance of unclassified variants in DNA (HNPCC) or Lynch syndrome is caused by DNA variations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6 In this review we discuss the various functional assays reported for the HNPCCassociated MMR proteins and the outcomes of these
Functional analysis helps to clarify the clinical We found that the MSH2(N25) mutant confers distinct biochemical defects on MSH2-MSH6, but does not have a significant effect on MSH2-MSH3. An unclassified variant (UV) in exon 1 of the MLH1
Sep 01, 2001 · All MLH1 or MSH2 variants were analyzed in the same host containing the same reporter gene and were eed from the same eion vector as the wild-type yeast gene. For all mutagenized genes, at least three independent clones were tested for
Functional analysis of human MLH1 and MSH2 missense Sep 01, 2001 · Functional analysis of human MLH1 and MSH2 missense variants and hybrid humanyeast MLH1 proteins in All MLH1 or MSH2 variants were analyzed in the same host containing the same reporter gene and were eed from the same eion vector as the wild-type yeast gene. For all mutagenized genes, at least three independent clones were
Integrated analysis of unclassified variants in mismatch The use of genetic tests to identify mutation carriers does not always give perfectly clear results, as happens when an unclassified variant is found. This study aimed to define the pathogenic role of 35 variants present in MSH2, MLH1, MSH6, and PMS2 genes identified in our 15-year case study.
Mario TOSI Cited by 5,127 of Université de Rouen, Mont-Saint-Aignan (UR) Read 126 publications Contact Mario TOSI
Massively parallel functional testing of MSH2 missense Jan 07, 2021 · We demonstrate that massively parallel functional assays can accurately measure the impacts of variants in the key Lynch syndrome gene MSH2. This functional effect map has the potential to enable more accurate classification of Lynch syndrome risk conferred by MSH2 variants, especially when rationally combined 55, 76 with other lines of evidence, 9 such as age of onset, polygenic risk scores,
ORIGINAL ARTICLE Functional analysis of MSH2 Feb 05, 2014 · MSH2-M813V was able to support all MMR functions similar to wild-type MSH2, whereas MSH2-Y165D and MSH2-Q690E showed partial defects. Conclusions Based on the results from our functional assays, we conclude that the MSH2-M813V variant is not disease causing. The MSH2-Y165D and MSH2-Q690E variants affect MMR function and are therefore