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Öğe Extremely Skewed X-Chromosome Inactivation Patterns in Women With Recurrent Spontaneous Abortion(Blackwell Publishing, 2006) Bağışlar, Sevgi; Üstüner, Işık; Cengiz, Bora; Söylemez, Feride; Akyerli, Cemaliye Boylu; Ceylaner, Serdar; Ceylaner, Gülay; Acar, Aynur; Özçelik, TayfunBackground: 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; chi(2) 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; chi(2) test). Conclusions: These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.