Sex ratio skewing of offspring in families with hereditary susceptibility to breast cancer

The function of BRCA1 is complex and includes roles in DNA damage repair, cell cycle control, regulation of transcription, and X chromosome inactivation. 1, 2 TSIX is thought to control X chromosome inactivation by blocking the accumulation of XIST on the active X chromosome. 3 BRCA1 co-localises with XIST inactive X chromosomes (Xi) and stabilises Xi. Because of this interaction, the loss of BRCA1 is associated with altered Xi chromatin structure and increased expression of silenced Xi genes. 1, 2 Mouse models have suggested a link between aberrant X chromosome inactivation and sex ratio skewing, with a bias towards male births when TSIX activity is abolished. 3 In addition, non-random X chromosome inactivation has been seen in BRCA1 mutation carriers with ovarian cancer. 4 With these data as background, a skewed sex ratio in offspring of BRCA1 mutation carriers was reported, 5 with a bias towards females, compared with offspring of women with BRCA2 mutations and those without mutations in either gene. [...]both small overall sample size and absence of 6174delT mutation carriers in the Spanish dataset may explain the discrepancies between these studies.