Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation-negative familial adenomatous polyposis
| Autor: | Jian Dong, Jun Yang, Wen Liang Li, Wei Qing Liu, Yan Xia Peng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Silent mutation Adult Male Cancer Research congenital hereditary and neonatal diseases and abnormalities Adolescent Adenomatous polyposis coli Adenomatous Polyposis Coli Protein Biochemistry Polymorphism Single Nucleotide Familial adenomatous polyposis DNA Glycosylases 03 medical and health sciences Exon Young Adult Germline mutation MUTYH familial adenomatous polyposis Genetics medicine Missense mutation Humans Genetic Predisposition to Disease Molecular Biology Alleles Genetic Association Studies Silent Mutation biology adenomatous polyposis coli Computational Biology Articles bioinformatics Exons Sequence Analysis DNA medicine.disease Exon skipping synonymous single nucleotide polymorphism mutY DNA glycosylase Alternative Splicing 030104 developmental biology Oncology Amino Acid Substitution biology.protein Molecular Medicine Female exon skipping |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Familial adenomatous polyposis (FAP) is an autosomal dominant‑inherited colorectal cancer. Recent advances in genetics have indicated that the majority of patients with FAP carry germline mutations of the adenomatous polyposis coli (APC) and mutY DNA glycosylase (MUTYH) genes. However, a large subset of families with a history of FAP have undetectable pathogenic alterations, termed APC/MUTYH mutation‑negative FAP. To investigate the germline mutations in the APC and MUTYH genes in Chinese patients with FAP, 13 unrelated patients were enrolled. Through genetic sequencing, four known pathogenic alterations (Lys1061LysfsTer2, Glu1309AspfsTer4, Arg283Ter and Ser1196Ter) of APC and two novel disease‑associated pathogenic mutations (Tyr152Ter and Ter522Gly) in MUTYH were identified in six individuals. For samples that did not present with pathogenic alterations, the functional effects of missense, synonymous and intronic mutations were analyzed using bioinformatics tools and databases. Bioinformatics prediction suggested that the synonymous mutation Tyr486Tyr in APC (APC∆486s) was likely a disease‑causing polymorphism and may have induced the exon skipping of APC. A hybrid mini‑gene assay was performed, which confirmed that the synonymous single nucleotide polymorphism APC∆486s induced major splicing defects with skipping of exon 12 in APC. The data of the present study suggested that the synonymous polymorphism APC∆486s was a potential pathogenic alteration that predisposed APC/MUTYH mutation‑negative patients to FAP. |
| Databáze: | OpenAIRE |
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