INVESTIGATION OF MOLECULAR GENETIC CAUSES OF EPILEPTIC ENCEPHALOPATHIES, NEURODEGENERATIVE DISEASES AND COMPLEX NEUROLOGICAL PHENOTYPES IN CHILDREN IN THE TURKESTAN REGION
Introduction. Hard-to-diagnose neurological disorders in children, including epileptic encephalopathies (EE), neurodegenerative diseases (NDD), and complex neurological phenotypes (CNP), are characterized by high genetic heterogeneity and clinical polymorphism. Deep phenotyping combined with exome sequencing can improve diagnostic accuracy and the identification of the molecular-genetic causes of these pathologies.
This study aims to improve diagnostics by conducting deep phenotyping of patients with EE, NDD, and CNP and identifying their molecular-genetic causes through exome sequencing among children in the Turkestan region.
Materials and Methods. A multicenter cross-sectional study was conducted on 79 children with suspected hereditary pathology, selected from a cohort of 250 patients with hard-to-diagnose neurological disorders. The diagnostic approach included clinical-neurological examination, deep phenotyping (precise and comprehensive analysis of phenotypic abnormalities) using HPO and Phenomizer, and exome sequencing to identify single nucleotide variants (SNVs) and copy number variations (CNVs). A frequency analysis was performed, calculating descriptive statistics for discrete data (mean values – arithmetic mean, relative values – intensive indicator) using IBM SPSS Statistics 29.0.1.0 software.
Results. Exome sequencing revealed genetic variations in 51.9% of patients: 87.8% SNVs and 12.2% CNVs. Pathogenic and likely pathogenic SNVs accounted for 75%. Deep phenotyping enabled the classification of patients into groups: EE (15.2%), NDD (49.4%), and CNP (35.4%) and identified common clinical manifestations (seizure syndrome – 68.3%, minor developmental anomalies – 60.7%, severe motor impairments – 46.2%). Reverse phenotyping confirmed the clinical significance of the identified mutations.
Conclusions. The results highlight the importance of deep phenotyping and exome sequencing in diagnosing hard-to-diagnose neurological disorders. The integration of these methods into clinical practice enhances diagnostic accuracy. It contributes to identifying the molecular mechanisms underlying pathologies, particularly in regions with limited access to molecular-genetic studies. This study contributes to global genomics by expanding the understanding of the molecular basis of rare neurological disorders.
Number of Views: 426
Category of articles:
Original article
Bibliography link
Yerkhojayeva N.H., Zharkinbekova N.A., Azhayev S.A., Rustemova S.A., Saifullaeva L.K., Rashidov E.B., Sandybayeva A.G., Kaiyrzhanov R.B. Investigation of molecular genetic causes of epileptic encephalopathies, neurodegenerative diseases and complex neurological phenotypes in children in the Turkestan region // Nauka i Zdravookhranenie [Science & Healthcare]. 2024. Vol.26 (6), pp. 94-105. doi 10.34689/SH.2024.26.6.012Related publications:
GENETIC VARIANTS IN LIPID-ASSOCIATED GENES IN THE KAZAKHSTANI COHORT WITH ATHEROSCLEROSIS AND HYPERTRIGLYCERIDEMIA
CLONAL HEMATOPOIESIS WITH INDETERMINATE POTENTIAL IN TET2 AND DNMT3A AMONG KAZAKHSTANI INDIVIDUALS WITH ATHEROSCLEROTIC DISEASE
PRELIMINARY ANALYSIS AND ASSESSMENT OF THE HEALTH STATUS OF THE DESCENDANTS OF PERSONS EXPOSED TO RADIATION, LIVING IN THE BESKARAGAI DISTRICT OF THE ABAY REGION
PRELIMINARY ANALYSIS OF THE HEALTH STATUS AND RADIATION DOSES OF RESIDENTS OF THE ABAY DISTRICT OF THE ABAY REGION, WHO ARE DESCENDANTS OF PERSONS EXPOSED TO RADIATION DUE TO NUCLEAR WEAPONS TESTS
TRENDS AND DISPARITIES IN CANCER MORBIDITY IN KAZAKHSTAN: A REGIONAL AND AGE-BASED ANALYSIS FOR 2014-2024