| http://purl.uniprot.org/citations/31784484 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31784484 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundInactivating mutations in the MLH1 DNA mismatch repair (MMR) gene underlie 42% of Lynch syndrome (LS) cases. LS is a cancer predisposition causing early onset colorectal and endometrial cancer. Nonsense and frameshift alterations unambiguously cause LS. The phenotype of missense mutations that only alter a single amino acid is often unclear. These variants of uncertain significance (VUS) hinder LS diagnosis and family screening and therefore functional tests are urgently needed. We developed a functional test for MLH1 VUS termed 'oligonucleotide-directed mutation screening' (ODMS).MethodsThe MLH1 variant was introduced by oligonucleotide-directed gene modification in mouse embryonic stem cells that were subsequently exposed to the guanine analogue 6-thioguanine to determine whether the variant abrogated MMR.ResutsIn a proof-of-principle analysis, we demonstrate that ODMS can distinguish pathogenic and non-pathogenic MLH1 variants with a sensitivity of >95% and a specificity of >91%. We subsequently applied the screen to 51 MLH1 VUS and identified 31 pathogenic variants.ConclusionODMS is a reliable tool to identify pathogenic MLH1 variants. Implementation in clinical diagnostics will improve clinical care of patients with suspected LS and their relatives."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.org/dc/terms/identifier | "doi:10.1136/jmedgenet-2019-106520"xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Dekker M."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Hofstra R.M.W."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Verhoef S."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Te Riele H."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Houlleberghs H."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Lusseveld J."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "Pieters W."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/author | "van Ravesteyn T."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/name | "J Med Genet"xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/pages | "308-315"xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/title | "Three-step site-directed mutagenesis screen identifies pathogenic MLH1 variants associated with Lynch syndrome."xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://purl.uniprot.org/core/volume | "57"xsd:string |
| http://purl.uniprot.org/citations/31784484 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31784484 |
| http://purl.uniprot.org/citations/31784484 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31784484 |
| http://purl.uniprot.org/uniprot/#_Q9JK91-mappedCitation-31784484 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31784484 |
| http://purl.uniprot.org/uniprot/#_Q8CAP8-mappedCitation-31784484 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31784484 |
| http://purl.uniprot.org/uniprot/#_Q8VDI4-mappedCitation-31784484 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31784484 |
| http://purl.uniprot.org/uniprot/#_Q9CTA7-mappedCitation-31784484 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31784484 |
| http://purl.uniprot.org/uniprot/Q9CTA7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31784484 |
| http://purl.uniprot.org/uniprot/Q8VDI4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31784484 |
| http://purl.uniprot.org/uniprot/Q8CAP8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31784484 |