#495 Genetic Insights into renal diseases in Armenian children

Abstract Background and Aims Advances in genetics have significantly enhanced our understanding of kidney diseases, enabling earlier diagnoses and more targeted interventions. This study aims to evaluate the diagnostic utility of genetic testing, conducted for the first time in Armenia, in children with kidney diseases. Method Since 2022, 25 patients aged 2–18 years (57.7% male) were included in this study. Genomic DNA was analyzed using next-generation sequencing (NGS). Target regions, including coding exons and corresponding exon-intron boundaries, were enriched with Twist Bioscience technology. Results The clinical presentations included isolated proteinuria (in 11), isolated hematuria (in 6), a combination of both (in 4), and steroid-resistant nephrotic syndrome (in 3). Additional findings were hearing deficits (in 4), thrombocytopenia (in 1), and behavioral issues (in 1). A positive family history of renal disease was noted in 9 patients. Kidney biopsies performed in 9 patients revealed minimal changes (in 2), FSGS (in 2), thinning of the basement membrane (in 3), and Alport syndrome (in 2). Genetic testing identified pathogenic variants in 18 patients (60%). Detected mutations included COL4A5 (in 6), COL4A3 (in 2), COL4A4 (in 1), COL4A3/A4 (in 1), AMN (in 1), CUBN (in 2), CLCN5 (in 1), OCRL (in 1), MYH9 (in 1), CFB (in 1), and monosomy X (n = 1). Final diagnoses comprised Alport syndrome (in 4; dominant in 3, X-linked in 1), Dent disease type 1 (in 1) and type 2 (in 1), Epstein syndrome (EPTS, in 1), Imerslund-Gräsbeck syndrome (IGS, in 3), atypical HUS (in 1), and Turner syndrome (in 1). Conclusion Genetic testing has proven instrumental in diagnosing kidney diseases in children, reducing the need for invasive procedures like kidney biopsy in many cases and expanding the spectrum of identified disorders. Importantly, some conditions (EPTS, IGS) were diagnosed for the first time in Armenia. Genetic findings facilitated personalized management and family counseling, underscoring the significance of this diagnostic approach.