Genetic profiling and molecular biology methods have made it possible to study the etiology of the end-stage organ disease that led to transplantation, the genetic factors of compatibility and tolerance of the transplant, and the pharmacogenetics of immunosuppressive drugs and allowed for the development of monitoring methods for the early assessment of allograft rejection. This study aims to report the design and baseline characteristics of an integrated personalized genetic approach in solid organ transplantation, including whole-exome sequencing (WES) and the monitoring of dd-cfDNA by dPCR. Preliminary results reported female recipients with male donors undergoing two pediatric and five adult kidney and three heart transplantations. WES revealed a pathogenic mutation in RBM20 and VUS in TTN and PKP2 in heart recipients, while kidney donors presented mutations in UMOD and APOL1 associated with autosomal-dominant kidney diseases, highlighting the risks requiring the long-term monitoring of recipients, donors, and their family members. %dd-cfDNA levels were generally stable but elevated in cadaveric kidney recipient and one pediatric patient with infectious complications and genetic variants in the ABCB1 and ABCC2 genes. These findings highlight the potential of combining genetic and molecular biomarker-based approaches to improve donor–recipient matching, predict complications, and personalize post-transplant care, paving the way for precision medicine in transplantation.

Background: Pediatric epilepsy is a clinically and genetically heterogeneous group of disorders, particularly in early-onset and syndromic presentations. Data integrating molecular findings with detailed clinical phenotyping remain limited in Kazakhstan and Central Asia. Methods: We conducted a retrospective, single-center, clinically selected, referral-based case series study of 31 pediatric patients evaluated at a tertiary center in Kazakhstan for epilepsy or epilepsy-associated neurodevelopmental disorders and found to have clinically relevant or potentially relevant genetic findings. Clinical records were reviewed for demographics, age at seizure onset, seizure semiology, developmental profile, EEG, MRI, extra-neurological features, treatment response, and family history. Variants were interpreted using ACMG-based criteria, and inheritance/segregation data were incorporated where available. Results: The cohort included 15 males and 16 females. Median seizure onset was 5.0 months (IQR 2.0–13.0), and 22/31 patients (71.0%) presented within the first year of life. Developmental delay/intellectual impairment was observed in 20/31 cases (64.5%), speech delay in 17/31 (54.8%), motor delay in 15/31 (48.4%), and hypotonia in 12/31 (38.7%). Variants were identified in 23 genes, including several variants with limited or no prior support in ClinVar or peer-reviewed reports. Ion channelopathies were the largest mechanistic group (12/31, 38.7%), followed by mitochondrial/metabolic disorders (6/31, 19.4%), mTOR pathway disorders (5/31, 16.1%), and neurodevelopmental/chromatin/transcriptional disorders (4/31, 12.9%). SCN1A was the most recurrent gene (8/31, 25.8%) and showed a broad phenotypic continuum from Dravet-compatible to non-Dravet presentations. EEG and MRI abnormalities were common and often syndromic in pattern. Treatment response was frequently partial or poor, although selected genotype-linked treatment observations were noted in PRRT2 (carbamazepine), PNPO (pyridoxine), and one SCN1A case (stiripentol). Conclusions: This study expands the clinicogenetic characterization of pediatric epilepsy cases with clinically relevant or potentially relevant genetic findings in Kazakhstan and highlights the value of integrated molecular, phenotypic, and segregation analysis in underrepresented populations.