Characterization of a germline splice site variant MLH1 c.678-3T>A in a Lynch syndrome family
| العنوان: | Characterization of a germline splice site variant MLH1 c.678-3T>A in a Lynch syndrome family |
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| المؤلفون: | Liying Zhang, Ester Borras, Margaret Sheehan, Kenneth Offit, Karen Cadoo, Ciyu Yang |
| المصدر: | Familial Cancer. 19:315-322 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, DNA, Complementary, 030105 genetics & heredity, Biology, DNA Mismatch Repair, Germline, 03 medical and health sciences, Exon, 0302 clinical medicine, Germline mutation, Genetics, medicine, Humans, splice, neoplasms, Germ-Line Mutation, Genetics (clinical), Aged, Reverse Transcriptase Polymerase Chain Reaction, Alternative splicing, Intron, nutritional and metabolic diseases, Exons, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Introns, digestive system diseases, Lynch syndrome, Pedigree, Oncology, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, DNA mismatch repair, RNA Splice Sites, MutL Protein Homolog 1 |
| الوصف: | Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome. Classification and interpretation of intronic variants, especially those outside the consensus ± 1 ~ 2 splice sites are challenging as it is uncertain whether such variants would affect splicing accuracy and efficiency. The assessment of the pathogenicity of splice site variants in MLH1 is further complicated by the various isoforms due to alternative splicing. In this report, we describe a 42-year-old female with Lynch syndrome who carries a germline variant, MLH1 c.678-3T>A, in the splice acceptor site of intron 8. Functional studies and semiquantitative analysis demonstrated that this variant causes a significant increase in the transcripts with exon 9 or exon 9 and 10 deletions, which presumably leads to premature protein truncation or abnormal protein. In addition, we also observed MSI-H and loss of MLH1 by IHC in patient’s tumor tissue. This variant also segregated with Lynch Syndrome related cancers in three affected family members. Based on these evidence, the MLH1 c.678-3T>A variant is considered pathogenic. |
| تدمد: | 1573-7292 1389-9600 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26d25ef1ccdfd2270cdf4698c0025e46Test https://doi.org/10.1007/s10689-020-00180-7Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....26d25ef1ccdfd2270cdf4698c0025e46 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15737292 13899600 |
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