Prevalence of CNVs on the X chromosome in patients with neurodevelopmental disorders
CNVs on the X chromosome were identified in 33 patients (2.8%). Duplications and triplications (27 cases) were four times more common than deletions (6 cases). In 74% of patients, CNVs were of maternal origin; in 10% they were of paternal origin; and in 16% they arose de novo. The frequency of skewed X inactivation among family members who were healthy carriers of pathogenic and likely pathogenic CNVs and variants of uncertain significance (VUSs) on the X chromosome was 23%. For the first time, we reported several CNVs, including a pathogenic microdeletion at Xq26.1q26.2 involving the ARHGAP36 gene and a microduplication at Xp22.2 involving the OFD1 gene, CONCLUSIONS: This study expands on the frequency and spectrum of CNVs in patients with NDDs. Pathogenic variants on the X chromosome were present in 15% of cases, LP in 12%, VUS in 57%, and LB in 16% of cases. Previously unreported CNVs aid in the identification of new structural variants and genes associated with X-linked intellectual disability. We propose to consider the X-chromosome inactivation status when assessing the pathogenetic significance of CNVs using the ACMG algorithm (American College of Medical Genetics).
Authors
- А. А. Кашеварова (ORCID: https://orcid.org/0000-0002-0716-4302)
- G. N. Seitova (ORCID: https://orcid.org/0000-0002-8421-1416)
- A. A. Agafonova (ORCID: https://orcid.org/0000-0003-0169-2072)
- Е. Н. Толмачева (ORCID: https://orcid.org/0000-0001-6427-3276)
- E. O. Belyaeva (ORCID: https://orcid.org/0000-0003-4956-5689)
- Ekaterina G. Ravzhaeva
- И. Н. Лебедев (ORCID: https://orcid.org/0000-0002-0482-8046)
- L. I. Minaycheva (ORCID: https://orcid.org/0000-0002-1752-2521)
- Л. П. Назаренко (ORCID: https://orcid.org/0000-0002-1861-433X)
- Nikolay Alekseevich Skryabin (ORCID: https://orcid.org/0000-0002-2491-3141)
- Elizaveta A. Fonova (ORCID: https://orcid.org/0000-0002-1338-5451)
- М. Е. Лопаткина (ORCID: https://orcid.org/0000-0002-7051-3472)
- V. V. Petrova (ORCID: https://orcid.org/0000-0003-4400-994X)
- Olga A. Salyukova
- D. A. Fedotov (ORCID: https://orcid.org/0000-0002-0295-3230)
- Oksana Yu. Vasilyeva (ORCID: https://orcid.org/0000-0001-5797-0014)
- S. L. Vovk
Institutions
- Russian Academy of Sciences (RU)
- Research Institute of Medical Genetics of Russian Academy of Medical Sciences (RU)
- Tomsk National Research Medical Center (RU)
Publication Details
- Journal
- Molecular Cytogenetics
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1186/s13039-025-00703-w
- Citations
- 1
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Nanomaterials Microdevices Research Center, Osaka Institute of Technology
- Russian Science Foundation
- Russian Academy of Sciences