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August 11, 2004

Sex Ratio Among the Offspring of

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2004;292(6):687-688. doi:10.1001/jama.292.6.687

To the Editor: It is possible that improper heterochromatinization of X chromosomes in XY bodies of male heterozygous BRCA1 carriers may lead such male sperm cells to be less viable, given that products of the BRCA1 gene are presumed to play a role in this process.1 Thus, male heterozygous carriers would be expected to have a greater proportion of female offspring. Indeed, de la Hoya et al2 reported an excess of females among the offspring of BRCA1 mutation carriers but no such sex-ratio distortion affects the offspring of BRCA2 carriers. However, these results might have reflected an ascertainment bias of carriers through affected females.3 Because penetrance is higher at younger ages in BRCA1 than in BRCA2 female carriers,4 this bias could be stronger in BRCA1 than in BRCA2-associated families.