ArticleBMC medical genetics2013
Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients.
Article in BMC medical genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Case report: Functional characterization of a novelFrontiers in genetics · 2023Article
- Classification of MSH6 Variants of Uncertain Significance Using Functional Assays.International journal of molecular sciences · 2021Review
- MLH1 intronic variants mapping to + 5 position of splice donor sites lead to deleterious effects on RNA splicing.Familial cancer · 2020Article
- Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk.Environmental science and pollution research international · 2018Article
- Genetic screening of the FLCN gene identify six novel variants and a Danish founder mutation.Journal of human genetics · 2017Article
- Functional Studies and In Silico Analyses to Evaluate Non-Coding Variants in Inherited Cardiomyopathies.International journal of molecular sciences · 2016Article
- Ovarian tumors related to intronic mutations in DICER1: a report from the international ovarian and testicular stromal tumor registry.Familial cancer · 2016Article
- Analysis of multiple cytokine polymorphisms in individuals with untreated deep carious lesions reveals IL1B (rs1143643) as a susceptibility factor for periapical lesion development.Journal of endodontics · 2015Article
- Aberrant methylation patterns in cancer: a clinical view.Biochemia medica · 2015Review
- Early-onset colorectal cancer: a sporadic or inherited disease?World journal of gastroenterology · 2014Review
- Review of Azoospermia.Spermatogenesis · 2014Review
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10 authors.
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Abstract
backgroundGerm-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance.
methodsIntronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay to asses the effect on splicing.
resultsWe describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732-2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T).
conclusionsIn conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members.
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