Cytogenomic epileptology

Molecular Cytogenetics

Review

Vseslav V. Ushanov¹  Konstantin A. Samochernyh²  Evgeny R. Barantsevich³  Yulia M. Zabrodskaya⁴  Darya A. Sitovskaya⁴  Alexandr P. Gerasimov⁵  Timur B.-A. Lobzhanidze⁶  Muslim M. Zhumatov⁶  Natalya E. Ivanova⁷  Irina A. Demidova⁸  Maria A. Zelenova⁸  Oksana S. Kurinnaia⁸  Svetlana G. Vorsanova⁸  Kirill S. Vasin⁸  Maria E. Iuditskaia⁸  Nikita S. Iakushev⁸  Alexey D. Kolotii⁸  Ivan Y. Iourov⁹ 

[1] Department of Neurosurgery, Almazov National Medical Research Centre, Saint Petersburg, Russia;Polenov Neurosurgical Institute, Almazov National Medical Research Centre, Saint Petersburg, Russia;Postgraduate Neurology and Manual Medicine Department, Pavlov First Saint-Petersburg State Medical University, Saint Petersburg, Russia;Research Laboratory of Pathomorphology of the Nervous System, Almazov National Medical Research Centre, Saint Petersburg, Russia;Research Laboratory of Pediatric Neurosurgery, Polenov Neurosurgical Institute, Almazov National Medical Research Centre, Saint Petersburg, Russia;Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia;Scientific Department of Polenov Neurosurgical Institute, Almazov National Medical Research Centre, Saint Petersburg, Russia;Yurov’s Laboratory of Molecular Genetics and Cytogenomics of the Brain, Mental Health Research Center, Moscow, Russia;Vorsanova’s Laboratory of Molecular Cytogenetics of Neuropsychiatric Diseases, Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University of the Russian Ministry of Health, Moscow, Russia;Yurov’s Laboratory of Molecular Genetics and Cytogenomics of the Brain, Mental Health Research Center, Moscow, Russia;Vorsanova’s Laboratory of Molecular Cytogenetics of Neuropsychiatric Diseases, Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University of the Russian Ministry of Health, Moscow, Russia;Department of Medical Biological Disciplines, Belgorod State University, Belgorod, Russia;

关键词: Brain;    Epilepsy;    Chromosomal abnormalities;    Chromosome instability;    Copy number variants;    Cytogenomics;    Epileptology;    Molecular cytogenetics;    Molecular neurocytogenetics;    Pathways;   

DOI  :  10.1186/s13039-022-00634-w

 received in 2022-12-19, accepted in 2022-12-20,  发布年份 2022

来源: Springer

【 摘 要 】

Molecular cytogenetic and cytogenomic studies have made a contribution to genetics of epilepsy. However, current genomic research of this devastative condition is generally focused on the molecular genetic aspects (i.e. gene hunting, detecting mutations in known epilepsy-associated genes, searching monogenic causes of epilepsy). Nonetheless, chromosomal abnormalities and copy number variants (CNVs) represent an important part of genetic defects causing epilepsy. Moreover, somatic chromosomal mosaicism and genome/chromosome instability seem to be a possible mechanism for a wide spectrum of epileptic conditions. This idea becomes even more attracting taking into account the potential of molecular neurocytogenetic (neurocytogenomic) studies of the epileptic brain. Unfortunately, analyses of chromosome numbers and structure in the affected brain or epileptogenic brain foci are rarely performed. Therefore, one may conclude that cytogenomic area of genomic epileptology is poorly researched. Accordingly, molecular cytogenetic and cytogenomic studies of the clinical cohorts and molecular neurocytogenetic analyses of the epileptic brain appear to be required. Here, we have performed a theoretical analysis to define the targets of the aforementioned studies and to highlight future directions for molecular cytogenetic and cytogenomic research of epileptic disorders in the widest sense. To succeed, we have formed a consortium, which is planned to perform at least a part of suggested research. Taking into account the nature of the communication, “cytogenomic epileptology” has been introduced to cover the research efforts in this field of medical genomics and epileptology. Additionally, initial results of studying cytogenomic variations in the Russian neurodevelopmental cohort are reviewed with special attention to epilepsy. In total, we have concluded that (i) epilepsy-associated cytogenomic variations require more profound research; (ii) ontological analyses of epilepsy genes affected by chromosomal rearrangements and/or CNVs with unraveling pathways implicating epilepsy-associated genes are beneficial for epileptology; (iii) molecular neurocytogenetic (neurocytogenomic) analysis of postoperative samples are warranted in patients suffering from epileptic disorders.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2022_35_Article_IEq419.gif

41116_2022_35_Article_IEq416.gif