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Clinical manifestations and X-chromosome inactivation in case of duplication of the Xq22.3q25 region

https://doi.org/10.25557/2073-7998.2024.11.63-66

Abstract

In most women, pathogenic variants on the X chromosome are not expressed or are expressed in a weakened form, since they are heterozygotes for the pathogenic variant and one of the X chromosomes in women is always inactivated. However, 15–20% of genes on the human X chromosome escape from inactivation and are expressed from both chromosomes. In an 11-year-old patient with encephalopathy of combined genesis and delayed speech development, a duplication on the long arm of the X chromosome was detected by standard cytogenetic analysis. Using chromosomal microarray analysis, we clarified the localization of the rearrangement: arr[GRCh38] Xq22.3q25(104563898_122794771)x3. The duplication have size of 18 Mb. The patient had extremely asymmetric inactivation of the X chromosome (95%). Nine genes that escape from inactivation are localized in the duplication region. An excessive dose of the ALG13 gene, pathogenic variants of which are associated with developmental encephalopathy and epileptic encephalopathy 36, may be the cause of the development of clinical symptoms in the patient.

About the Authors

E. N. Tolmacheva
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

 Ekaterina N. Tolmacheva

10, Naberejnaya Ushaiki, Tomsk, 634050



A. A. Kashevarova
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



N. N. Sukhanova
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



A. А. Agafonova
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



L. I. Minaycheva
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



E. A. Fonova
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



O. Yu. Vasilyeva
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



D. A. Fedotov
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



I. N. Lebedev
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation

10, Naberejnaya Ushaiki, Tomsk, 634050



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Review

For citations:


Tolmacheva E.N., Kashevarova A.A., Sukhanova N.N., Agafonova A.А., Minaycheva L.I., Fonova E.A., Vasilyeva O.Yu., Fedotov D.A., Lebedev I.N. Clinical manifestations and X-chromosome inactivation in case of duplication of the Xq22.3q25 region. Medical Genetics. 2024;23(11):63-66. (In Russ.) https://doi.org/10.25557/2073-7998.2024.11.63-66

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ISSN 2073-7998 (Print)