Epigenetic modification of X-linked CNV in norm and pathology

Introduction: The process of the X chromosome inactivation in females is random, while preferential inactivation of one of the parental homologues may indicate the presence of mutations in it and lead to the development of hereditary pathology in the offspring. Aim: Identification of X-linked loci the epigenetic modifications of which can compensate for the development of a pathological phenotype. Materials and methods: 111 women with miscarriage and 47 women with no history of spontaneous abortions were examined. Using methyl-sensitive PCR and array comparative genomic hybridization, X-linked copy number variations (CNV) were analyzed in blood lymphocytes of women with an extreme skewing of X chromosome inactivation. Results: The incidence of extreme skewing of X chromosome inactivation in women with miscarriage and in the control group was 9 and 4%, respectively (p>0.05). In 8 women with an extreme skewing of inactivation and miscarriage X-linked CNVs at Xp11.23, Xp22.33, Xq24 and Xq28 were identified and their gene content was analyzed. It was shown that most of the identified CNVs were in one way or another associated with the development of X-linked forms of mental retardation. Conclusions: The epigenetic modification of X-linked CNVs compensates for their phenotypic manifestation in female carriers. At the same time, the absence of compensatory epigenetic/

асимметричная инактивация Х-хромосомы, СNV, невынашивание беременности, skewed X-chromosome inactivation, CNV, miscarriage

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