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 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.
Lanasa
M C
MC
Biochemistry and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Hogge
W A
WA
D000026:Abortion, Habitual / Q000235:genetics*; D002869:Chromosome Aberrations; D004303:Dosage Compensation, Genetic; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D011247:Pregnancy; D014960:X Chromosome