Saya Amangeldikyzy

Epilepsy and autism spectrum disorder (ASD) frequently co-occur and share complex genetic determinants. However, molecular diagnosis remains challenging because of incomplete penetrance, variable expressivity, and the limited representation of Central Asian populations in genomic reference databases. This case report describes a Kazakhstani family with 9-year-old monozygotic twin girls who developed focal seizures with secondary generalization at approximately one year of age and were subsequently diagnosed with ASD. Family-based whole-exome sequencing was performed for both affected twins and their clinically unaffected, non-consanguineous parents. No pathogenic or likely pathogenic variant explaining the shared epilepsy–ASD phenotype was identified. A paternally inherited NPRL3 missense variant, c.121A>G (p.Lys41Glu), was considered biologically plausible because of the established association of NPRL3 with focal epilepsy. However, it remained a variant of uncertain significance (VUS), was not reported in the queried gnomAD dataset, and had an AlphaMissense score of 0.14. Additional heterozygous VUS were identified in SPTBN4, ANK2, VPS33A, SLC25A46, and GFM1. Two ZC2HC1C variants inherited from different parents supported a possible biallelic hypothesis, but their clinical significance was uncertain. We interpreted a heterozygous pathogenic ALDOB variant as an incidental carrier finding unrelated to the presenting phenotype. This case illustrates the distinction between candidate variants and a molecular diagnosis. Further evaluation may include periodic exome reanalysis, copy-number analysis, genome sequencing, and targeted validation where justified. Broader population reference resources could improve variant interpretation in Kazakhstan.

Introduction. Neurological disorders (ND) are diseases that affect both the central nervous system (CNS) and peripheral nervous system (PNS). The aetiology of neurological disorders is highly diverse and may involve genetic, environmental, metabolic, infectious, immune-mediated, and acquired factors. Epilepsy, cerebral palsy (CP), and autism spectrum disorder (ASD) are clinically and genetically heterogeneous neurological and neurodevelopmental conditions that frequently manifest during childhood. Although these disorders have distinct core clinical features, considerable phenotypic overlap and comorbidity are observed, suggesting they may share underlying genetic and molecular mechanisms. Methods. Recruitment of the family, interview and clinical data acquisition, as well as blood sample acquisition, took place at the “National Center for Children's Rehabilitation” NJSC. DNA was isolated using commercially available kits. Whole-exome sequencing (WES) was performed using DNA Prep with Exome 2.0 Plus Enrichment Kit on the NovaSeq-6000 platform. All sequencing reads were mapped to the human reference genome assembly GRCh38 (hg38) using the DRAGEN Platform. Variant annotation was performed using VEP release 116.0. Results. We recruited a family with multiple neurological conditions. The parents were a Kazakh male and female with no family history of neurological or neurodevelopmental conditions. Marriage is non-consanguineous. There are three probands in the family diagnosed with autism spectrum disorder (ASD), focal symptomatic epilepsy, and (ASD) and ataxic cerebral palsy (CP), respectively. Bioinformatic analysis revealed pathogenic/likely pathogenic variants in IL10, CDKN2B, GALC, and SLC12A3 genes. In addition, we identified variants of uncertain significance (VUS), loss-of-function (LoF), compound heterozygous, X-linked, and single de novo mutation, in many genes involved in neurological or neurodevelopmental conditions. Conclusion. Overall, our findings demonstrate substantial genetic heterogeneity within a single family presenting with different neurological and neurodevelopmental phenotypes. The results highlight the challenges of interpreting rare and uncertain variants identified by whole-exome sequencing and emphasize the importance of integrating variant classification, inheritance patterns, segregation analysis, clinical phenotype, and available gene–disease evidence. Further functional studies and accumulation of additional clinical cases will be required to determine the contribution of the identified candidate variants to autism spectrum disorder, epilepsy, and other neurological manifestations in this family.

Introduction. Elite athletes undergo regular high-intensity training to maintain fitness and improve performance. Training overload is necessary to achieve significant results. However, failure to balance training and recovery can lead to overtraining syndrome. To prevent this, regular monitoring of biochemical markers is required to assess the body's adaptive processes. Aim of the study. Comparative analysis of blood biochemical parameters in Olympic athletes of Kazakhstan to assess training load effects and prevent overtraining syndrome Methods. A biochemical analysis was conducted to measure levels of creatinine, creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in Olympic athletes. Results. Significant differences in biochemical markers were observed among sports disciplines. Creatinine (p<0.001), alkaline phosphatase (p<0.001), AST (p<0.001), CK (p=0.008), and LDH (p<0.001) levels differed significantly between groups, whereas ALT showed no significant variation (p=0.191). Post hoc analyses revealed higher creatinine levels in weightlifters and freestyle wrestlers, elevated alkaline phosphatase levels in combat sport athletes, and significant sport-specific differences in AST, CK, and LDH, reflecting variations in muscle metabolism and training-related physiological adaptation. Conclusion. These findings underscore the importance of monitoring biochemical markers in elite athletes to prevent overtraining and optimize the training process. Keywords: biochemical markers, sports medicine, creatine kinase, lactate dehydrogenase, athletes of Kazakhstan.

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