X chromosome defects as an etiology of recurrent spontaneous abortion

Abstract

Recurrent spontaneous abortion is a significant problem in women's health, yet it remains a poorly understood phenomenon. Many cases of recurrent spontaneous abortion defy diagnosis, and we predict that a subset of these unexplained cases are caused by previously unknown, recessively inherited genetic causes. Here, we provide background on known genetic factors that contribute to spontaneous abortion and describe a novel X chromosome-based genetic mechanism that may be an important cause of recurrent spontaneous abortion. Recessively inherited defects on the human X chromosome would cause no symptoms in carrier females but would be lethal in utero to male conceptions that receive the defective X. Through investigation of the basic biology of the X chromosome, we propose that the female carriers of such traits can be identified through the molecular finding of skewed X chromosome inactivation. Furthermore, we have observed an association between skewed X chromosome inactivation and recurrent pregnancy loss, supporting the hypothesis that X chromosome defects may be an important, previously unknown cause of recurrent pregnancy loss.