Extremely skewed X-chromosome inactivation patterns in women with recurrent spontaneous abortion


  • This manuscript was presented in European Human Genetics Conference, 12–15 June 2004, Munich, Germany as a poster presentation.

  • DOI: 10.1111/j.1479-828X.2006.00622.x

: Professor Tayfun Ozcelik, Department of Molecular Biology and Genetics, B-242, Bilkent University, Bilkent, Ankara 06800, Turkey. Email: tozcelik@fen.bilkent.edu.tr


Background:  The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of recurrent spontaneous abortion (RSA) but the results obtained were conflicting.

Aims:  We therefore investigated the XCI patterns in peripheral blood DNA obtained from 80 patients who had RSA and 160 age-matched controls.

Methods:  Pregnancy history, age, karyotype, and disease information was collected from all subjects. The methylation status of a highly polymorphic cytosine-adenine-guanine repeat in the androgen-receptor (AR) gene was determined by use of methylation-sensitive restriction enzyme HpaII and polymerase chain reaction.

Results:  Skewed XCI (> 85% skewing) was observed in 13 of the 62 patients informative for the AR polymorphism (20.9%), and eight of the 124 informative controls (6.4%) (P = 0.0069; χ2 test). More importantly, extremely skewed XCI, defined as > 90% inactivation of one allele, was present in 11 (17.7%) patients, and in only two controls (P = 0.0002; χ2 test).

Conclusions:  These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.