RT info:eu-repo/semantics/article
T1 Unraveling the molecular effect of a rare missense mutation in BRIP1 associated with inherited breast cancer
A1 Velázquez Pérez, Carolina
A1 Esteban Cardeñosa, Eva
A1 Lastra, Enrique
A1 Abella, Luis E.
A1 de la Cruz, Virginia
A1 Domínguez Lobatón, María Carmen
A1 Duran Dominguez, María Mercedes
A1 Infante Sanz, María Del Mar
AB BRIP1 is a component of the Fanconi Anemia/BRCA pathway responsible for DNA reparation via helicase activity. Some heterozygous variants in BRIP1 could contribute to Hereditary Breast Cancer through a defective DNA repair. The clinical utility of BRIP1 mutations in a familial cancer context is compromised by the conflicting interpretation of “variants of uncertain significance” (VUS). Defining the clinical significance of variants identified in genetic tests is a major challenge; therefore, studies that evaluate the biological effect of these variants are definitely necessary. To contribute to this purpose, we have characterized the variant c.550G>T of BRIP1, a missense mutation with little evidence about its pathogenicity. Since Human Splicing FinderTM predicts the creation of a new exonic splicing enhancer site we decided to perform cDNA analysis revealing that the c.550G>T mutation located in exon 6 led to an aberrant transcript causing exon 5 skipping. Our results demonstrate that the c.550G>T BRIP1 variant disrupts normal splicing, causing exon 5 skipping. Considering that the exon 5 encodes the helicase domain of BRIP1, it is expected an alteration of the function. This finding enhances the interpretation of this VUS, suggesting a potential pathogenic effect.
PB Wiley
SN 0899-1987
YR 2019
FD 2019-01
LK https://uvadoc.uva.es/handle/10324/73281
UL https://uvadoc.uva.es/handle/10324/73281
LA spa
NO Molecular Carcinogenesis,2019 Jan;58(1):156-160
DS UVaDOC
RD 09-abr-2025