X-chromosome inactivation patterns in Korean women with idiopathic recurrent spontaneous abortion

Abstract

Recurrent spontaneous abortion (RSA) defines as two or more consecutive losses at < or = 20 weeks of gestation and affects an estimated 1 of every 100 couples wishing to have children. However, it remains a poorly understood phenomenon. Recent reports observed a significant association between highly skewed X chromosome and RSA, supporting that X chromosome inactivation might be an important and previously unknown cause of RSA. X-inactivation pattern, using polymeric X-linked women with idiopathic RSA and 80 control subjects with a single successful pregnancy and no history of spontaneous abortion. The ratio of heterozygotes was 68.2% (45/66) in women with RSA and 67.5% (54/80) in control group. Among 45 informative RSA cases, only 1 (2.2%) woman showed extreme skewed X inactivation (> or = 90%) and 4 (8.9%) had mild skewed inactivation (> or = 85%). In 54 heterozygous control subjects, 5 (9.3%) women showed extreme skewed X inactivation and 7 (13.0%) had mild one. The frequency of skewed X inactivation between RSA patients and control group was not significantly different (p>0.05). This finding suggests that skewed x chromosome be not associated with unexplained RSA patients.

Fig. 1

Comparison of age patterns in patients with RSA and control females. No significant difference in age was observed between two groups (p=0.457)

Fig. 2

Representative example of PCR analysis in three cases with RSA by AR gene. (A) RSA30 (skewed 56.95%); (B) RSA32 (skewed 88.61%); (C) RSA48, showing homozygosity (not informative); (D) normal male. Lane - and + show PCR amplification before and after HpaII digestion, respectively.

Fig. 3

Frequency distribution of X inactivation in 45 heterozygous RSA cases and 54 control females. The skewing values are expressed as the percentage ratio of the predominantly inactive allele to the predominantly active allele and are arranged into 10% intervals.