Аннотация
Background: Alport syndrome is a hereditary disorder caused by defects in the type IV collagen network. Although exon variants are primarily associated with Alport syndrome, the clinical significance of intronic variants remains incompletely characterized. The aim of this study was to characterize the clinical and molecular features of a familial case of Alport syndrome associated with the intronic variant c.1588-2A>G and to assess its impact using in silico tools. Case description: Two affected siblings presented with hematuria, proteinuria, and renal biopsy demonstrated focal global and segmental glomerulosclerosis, findings consistent with Alport syndrome. Whole-exome sequencing was subsequently performed in patients. The variant (NM_033380.2, c.1588-2A>G) in intron 23 of the COL4A5 gene was identified in both probands. SpliceAI analysis demonstrated a complete loss of the canonical acceptor site and a high probability of cryptic site activation. Conclusion: The evidence suggests a likely pathogenic role of the COL4A5 c.1588-2A>G variant in Alport syndrome.