X chromosome defects as an etiology of recurrent spontaneous abortion

Recurrent spontaneous abortion is a significant problem in women's health, yet it remains a poorly understood phenomenon. Many cases of recurrent spon taneous abortion defy diagnosis, and we predict that a subset of these unex plained cases are caused by previously unknown, recessively inherited genet ic causes. Here, we provide background on known genetic factors that contri bute to spontaneous abortion and describe a novel X chromosome-based geneti c mechanism that may be an important cause of recurrent spontaneous abortio n. Recessively inherited defects on the human X chromosome would cause no s ymptoms in carrier females but would be lethal in utero to male conceptions that receive the defective X. Through investigation of the basic biology o f the X chromosome, we propose that the female carriers of such traits can be identified through the molecular finding of skewed X chromosome inactiva tion. Futhermore, we have observed an association between skewed X chromoso me inactivation and recurrent pregnancy loss, supporting the hypothesis tha t X chromosome defects may be an important, previously unknown cause of rec urrent pregnancy loss.