Hereditary diseases in the Mozdok region of the Republic of North Ossetia – Alania

Introduction. The global burden of hereditary pathologies (HP) continues to rise, driven by advancements in molecular diagnostics, expanded phenotype characterization (7,586 disorders cataloged in OMIM), and increased accessibility of genetic testing in public healthcare. This study investigates the prevalence and spectrum of HPs in the ethnically diverse population of Mozdok District, Republic of North Ossetia-Alania (RNO-A), to elucidate genetic disease patterns across distinct demographic groups.
Methods. A population-based genetic epidemiological study was conducted among 90,244 individuals in Mozdok District, comprising three primary ethnic groups: Russians (48.95%, n = 44,172), Kumyks (17.87%, n = 16,123), and Ossetians (8.69%, n = 7,841), alongside 13 smaller groups (24.49%, n = 22,108). Utilizing a methodology developed by the Research Centre for Medical Genetics (RCMG), the burden of HPs (per 1,000 individuals) was calculated, and disease diversity was analyzed for autosomal dominant (AD), autosomal recessive (AR), and X-linked disorders. Comparative analyses of prevalence across ethnic groups employed chi-squared tests and Fisher’s exact test. Confirmatory genetic testing (high-throughput sequencing, Sanger sequencing, MLPA) was performed in select cases.
Results. A total of 333 patients (from 241 families) were diagnosed with 107 distinct HPs. The cumulative HP prevalence was 3.79 per 1,000 individuals (1:264), with significant ethnic variation: Kumyks exhibited the highest burden (6.76/1,000; 1:148), followed by Ossetians (4.98/1,000; 1:201) and Russians (2.31/1,000; 1:433). Thirty-three frequent HPs (prevalence ≥1:30,000) accounted for 74.43% of cases (n = 248), including 13 AD, 10 AR, and 10 X-linked disorders. Genetic confirmation was achieved in 74.59% of tested cases (n = 91/122).
Conclusions. This study highlights substantial ethnic disparities in HP prevalence within Mozdok District, ranging from 2.01/1,000 in Russians to 9.49/1,000 in Kumyks. Each ethnic group demonstrated a unique profile of frequent HPs, reflecting founder effects or consanguinity patterns. These findings align with trends observed in other multi-ethnic populations and underscore the

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