BRCA2 minor transcript lacking exons 4-7 supports viability in mice and may account for survival of humans with a pathogenic biallelic mutation

This study provides the first in vivo evidence of the functional significance of a minor transcript of BRCA2 that can play a major role in the survival of humans who are homozygous for a clearly pathogenic mutation. Our results highlight the importance of assessing protein function restoration by premature truncating codon bypass by alternative splicing when evaluating the functional significance of variants such as nonsense and frame-shift mutations that are assumed to be clearly pathogenic. Our findings will impact not only the assessment of variants that map to this region, but also influence counseling paradigms and treatment options for such mutation carriers.

Source: Human Molecular Genetics - October 12, 2016 Category: Genetics & Stem Cells Authors: Thirthagiri, E., Klarmann, K. D., Shukla, A. K., Southon, E., Biswas, K., Martin, B. K., North, S. L., Magidson, V., Burkett, S., Haines, D. C., Noer, K., Matthai, R., Tessarollo, L., Loncarek, J., Keller, J. R., Sharan, S. K. Tags: ARTICLES Source Type: research