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Inter-Tissue Gonosomal Mosaicism in Patients with Disorders of Sex Development, Associated with Abnormalities of Gonadal Differentiation

  • HUMAN GENETICS
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Abstract

We present results of the study to identify gonosomal mosaicism and examine its inter-tissue variability in peripheral blood lymphocytes, buccal epithelium, and gonadal tissue in patients with disorders of sex development (DSD) associated with sex chromosome abnormalities (gonosomal DSD, n = 8) and gonad differentiation anomalies (46,XY DSD, n = 10). The study used a set of methods for analyzing individual cells: karyoty** and interphase FISH. According to the study results, gonosomal mosaicism was detected in 12 (67%) of the 18 examined patients. Cryptic, isolated by gonadal tissue, somatic mosaicism with 45,X cell line was detected in 4/10 46,XY DSD group patients. True inter-tissue mosaicism with two cell lines, one of which 45,X, was detected in 8/8 gonosomal DSD group patients. We propose using a new approach for mosaicism examination and quantifying mosaic cell lines variability. For this purpose, the coefficient of variation (CV) was used, the range of detected values was from 2.3 to 49%. In accordance with the obtained CV values, the inter-tissue variability was estimated as low, moderate or high. The correlation analysis revealed a statistically significant (p < 0.1) inverse correlation between Prader's stage and 45,X cell line percentage in lymphocytes, buccal epithelium, and gonadal tissue, as well as a direct correlation between the 45,X cell line presence in one of the tissues and its presence in other tissues. The search for mosaicism in tissues of different histogenesis origin using a set of methods for analyzing individual cells allows us to get a more complete picture of the gonosomal constitution and reveal a hidden imbalance, which is very important in examining patients with DSD. We proposed and used in this study the coefficient of variation (CV), which is a convenient statistical metric for quantifying the variability of cell lines in different tissues of a single patient and a step towards standardizing the results of genetic studies.

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Funding

This work was carried out without attracting additional funding from third parties.

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Authors and Affiliations

  1. Moscow Regional Clinical Research Institute, 129110, Moscow, Russia

    N. V. Oparina

  2. Saratov State Medical University, 410012, Saratov, Russia

    N. Yu. Raygorodskaya

  3. Russian Medical Academy of Continuous Professional Education, 125993, Moscow, Russia

    O. Yu. Latyshev, L. N. Samsonova & E. A. Volodko

  4. State University of Management, 109542, Moscow, Russia

    S. A. Suyazova

  5. Research Centre for Medical Genetics, 115522, Moscow, Russia

    V. B. Chernykh

Authors
  1. N. V. Oparina
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  2. N. Yu. Raygorodskaya
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  3. O. Yu. Latyshev
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  4. L. N. Samsonova
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  5. E. A. Volodko
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  6. S. A. Suyazova
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All authors made a significant contribution to the preparation of the article and read and approved the final version.

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Correspondence to N. V. Oparina.

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Conflict of interest. The authors declare that they have no conflict of interests.

Statement of compliance with standards of research involving humans as subjects. All procedures carried out in a study with the participation of people comply with the ethical standards of the institutional and/or national research ethics committee and the 1964 Helsinki Declaration and its subsequent changes or comparable standards of ethics.

Informed voluntary consent was obtained from each of the participants in the study.

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Translated by A.A. Kashevarova

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Oparina, N.V., Raygorodskaya, N.Y., Latyshev, O.Y. et al. Inter-Tissue Gonosomal Mosaicism in Patients with Disorders of Sex Development, Associated with Abnormalities of Gonadal Differentiation. Russ J Genet 57, 1312–1321 (2021). https://doi.org/10.1134/S1022795421110107

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