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

Bagislar, S.
Ustuner, I.
Cengiz, B.
Soylemez, F.
Akyerli, C. B.
Ceylaner, S.
Ceylaner, G.
Acar, A.
Ozcelik, T.
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Wiley-Blackwell Publishing Asia

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 (> 8 5% 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; χ 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; χ 2 test). Conclusions: These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.

Androgen receptor, Mosaicism, Mutation, Recurrent abortion, X-chromosome inactivation, Androgen receptor, DNA, Adult, Allele, Article, Controlled study, Female, Gene mutation, Genetic analysis, Genetic polymorphism, Genetic susceptibility, Human, Karyotype, Major clinical study, Pathogenesis, Polymerase chain reaction, Priority journal, Protein methylation, Receptor gene, Recurrent abortion, Risk factor, Sex chromosome mosaicism, Spontaneous abortion, Statistical analysis, Trinucleotide repeat, X chromosome inactivation, Abortion, Habitual, Alleles, DNA, DNA Methylation, Humans, Mosaicism, Polymorphism, Genetic, Pregnancy, Receptors, Androgen, X Chromosome Inactivation