ArticleJournal of medical genetics2006
Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family.
Article in Journal of medical genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition.International journal of molecular sciences · 2020Article
- Review
- Exon identity crisis: disease-causing mutations that disrupt the splicing code.Genome biology · 2014Review
- A compensatory effect upon splicing results in normal function of the CYP2A6*14 allele.Pharmacogenetics and genomics · 2013Article
- Article
- Novel GUCA1A mutations suggesting possible mechanisms of pathogenesis in cone, cone-rod, and macular dystrophy patients.BioMed research international · 2013Article
- The exon 29 c.3535A>T in the alpha-2-macroglobulin gene causing aberrant splice variants is associated with mastitis in dairy cattle.Immunogenetics · 2012Article
- The MLH1 2101C>A (Q701K) variant increases the risk of gastric cancer in Chinese males.BMC gastroenterology · 2011Article
- Article
- Transposable elements in disease-associated cryptic exons.Human genetics · 2010Article
- Genomic features defining exonic variants that modulate splicing.Genome biology · 2010Article
- Article
- Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics.Human mutation · 2009Article
- Prediction and assessment of splicing alterations: implications for clinical testing.Human mutation · 2008Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA 3 bp deletion located at the 5' end of exon 3 of MLH1, resulting in deletion of exon 3 from RNA, was recently identified. HYPOTHESIS: That this mutation disrupts an exon splicing enhancer (ESE) because it occurs in a purine-rich sequence previously identified as an ESE in other genes, and ESEs are often found in exons with splice signals that deviate from the consensus signals, as does the 3' splice signal in exon 3 of MLH1.
designThe 3 bp deletion and several other mutations were created by polymerase chain reaction mutagenesis and tested using an in vitro splicing assay. Both mutant and wild type exon 3 sequences were cloned into an exon trapping vector and transiently expressed in Cos-1 cells.
resultsAnalysis of the RNA indicates that the 3 bp deletion c.213_215delAGA (gi:28559089, NM_000249.2), a silent mutation c.216T-->C, a missense mutation c.214G-->C, and a nonsense mutation c.214G-->T all cause varying degrees of exon skipping, suggesting the presence of an ESE at the 5' end of exon 3. These mutations are situated in a GAAGAT sequence 3 bp downstream from the start of exon 3.
conclusionsThe results of the splicing assay suggest that inclusion of exon 3 in the mRNA is ESE dependent. The exon 3 ESE is not recognised by all available motif scoring matrices, highlighting the importance of RNA analysis in the detection of ESE disrupting mutations.
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