Parental Origin of the Retained X Chromosome in Monosomy X Miscarriages and Ongoing Pregnancies

To assess the distribution of the parental origin of the retained X chromosome in monosomy X, either in miscarriages or in ongoing pregnancies.

The parental origin of the X chromosome was determined in monosomy X pregnancies, either miscarriages or ongoing pregnancies. Microsatellite marker patterns were compared between maternal and fetal samples by quantitative fluorescence polymerase chain reaction. Distributions of maternally and paternally derived X chromosome were assessed in miscarriages and in ongoing pregnancies using two-tailed Fisher exact test.

Forty monosomy X pregnancies were included in the study: 26 miscarried at 5-16 weeks, and 14 ongoing pregnancies were diagnosed at 11-20 weeks. The retained X chromosome was maternally derived in 67% of the cases. In miscarriages, maternal and paternal X chromosome were retained in a similar proportion (54% [95% CI: 35-73%] vs. 46% [95% CI: 27-65%]), while in ongoing pregnancies, the maternal rate was 13 times higher (93% [95% CI: 79-100%)] vs. 7% [95% CI: 0-20%]).

The retained X chromosome in individuals with monosomy X should theoretically be maternally derived in 2/3 of the cases. Our study suggests a preferential early miscarriage in pregnancies with a retained paternally derived X chromosome. This may explain the observation that 75-90% of individuals with monosomy X retain the maternal X chromosome.