Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family
| Autor: | Hela Sassi, Rym Meddeb, Mediha Trabelsi, Samia Hannachi, Neila Belguith, Imen Abbes, Khaled Rahal, Karima Mrad, Amel Mezlini, Ridha M’rad |
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| Rok vydání: | 2021 |
| Předmět: |
Proband
Genetics Mutation endocrine system diseases Genetic counseling Point mutation Biology medicine.disease medicine.disease_cause Germline Frameshift mutation Germline mutation medicine General Earth and Planetary Sciences skin and connective tissue diseases Ovarian cancer General Environmental Science |
| Zdroj: | Clinical Oncology and Research. :1-7 |
| ISSN: | 2613-4942 |
| DOI: | 10.31487/j.cor.2021.01.03 |
| Popis: | Inherited predisposition to breast and ovarian cancer are most frequently due to germline mutations in the main genes BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185). These inactivating mutations, essentially frameshift and nonsense variation, occurs mainly across conserved regions. The aim of the present study is to report a novel germline BRCA1 mutation identified in a Tunisian family case with early onset of breast and ovarian cancer and to evaluate the genotype phenotype correlation. The proband had high-grade tumors, invasive unilateral ductal carcinoma developed at the age of 38 and a serous ovarian adenocarcinoma after a gap of twelve years. The molecular analysis revealed a novel heterozygous nonsense BRCA1 mutation NM_007294.4: c.915T>A p.(C305*) in the proband and her daughter. This mutation leads to a truncated protein which pathogenicity was validated by bioinformatics tools. This variant is subject to nonsense-mediated mRNA decay. We also underlined the immunohistochemistry usefulness by lack of expression of BRCA1 protein in paraffin embedded breast tumor contrasting with normal tissue. Clinical and pathological data tend to be homogeneous and led to the conclusion that there is a genotype phenotype correlation in BRCA1, an element that must be taken into account in genetic counselling. Conclusively, we are the first to report this novel BRCA1 germline likely deleterious variant extending the molecular and clinical spectrum of BRCA1 pathogenic point mutations. Further in vitro functional experiments needs to be established. High-risk individuals carrying this BRCA1 mutation benefit from preventive measures to reduce morbidity. |
| Databáze: | OpenAIRE |
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