Double frameshift mutations in APC and MSH2 in the same individual
| Autor: | Jean-Louis Blouin, Zuzana Dobbie, Marie-Anne Brundler, Celia D. DeLozier, Pierre Hutter, Claudine Rey Berthod, William D. Foulkes, Claudio Soravia, Eviano Arrigoni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Proband
Adult Male Pathology medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Genes APC Adenoma Adenomatous polyposis coli Adenomatous Polyposis Coli/diagnosis/genetics/surgery Gene mutation Frameshift mutation Familial adenomatous polyposis Diagnosis Differential Germline mutation medicine Humans ddc:576.5 Genetic Predisposition to Disease Frameshift Mutation Colectomy Germ-Line Mutation Colorectal Neoplasms Hereditary Nonpolyposis/diagnosis/genetics/surgery biology ddc:617 business.industry Gastroenterology medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis digestive system diseases Pedigree MutS Homolog 2 Protein Adenomatous Polyposis Coli MSH2 biology.protein business MutS Homolog 2 Protein/genetics |
| Zdroj: | International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery, Vol. 20, No 5 (2005) pp. 466-470 International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery, Vol. 21, No 1 (2006) pp. 79-83 |
| ISSN: | 0179-1958 |
| Popis: | Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (less than ten) was not typical of polyposis; therefore, the diagnosis of HNPCC was entertained. Microsatellite instability analyses were performed on peripheral blood and biopsy of a right-sided dysplastic adenoma. The tumour tissue showed high-grade instability, and subsequently, immunohistochemistry showed that neither MSH2 nor MSH6 proteins were expressed in tumour cells. Prophylactic colectomy was performed, and an adenocarcinoma developing within the adenoma was diagnosed (pT1N0). Genomic DNA analysis revealed a novel mutation in MSH2 as a frameshift mutation in exon 7 (c.1,191_1,192dupG). Both parents of the proband were analyzed for MSH2 and APC mutations, and in the father, a truncating mutation in exon 15 of APC was identified as del3471-3473GAGA. This mutation was found to be present in the proband. His mother was found to bear the MSH2 exon 7 mutation. At follow-up, the proband was diagnosed with fundic, antral and duodenal adenomas (one fundic adenoma showed low-grade dysplasia). Several tubular rectal adenomas with low-grade dysplasia were excised. The patient later developed an intra-abdominal desmoid tumour. |
| Databáze: | OpenAIRE |
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