Case Report: a novel non-canonical splice site variant in COL4A5 in a patient with Alport syndrome

Alport syndrome is a genetically heterogeneous disorder caused by mutations in type IV collagen genes, clinically characterized by progressive renal function deterioration. The article describes a case of a pediatric patient with Alport syndrome and his mother, both carrying a novel splicing variant in the COL4A5 gene. The patient presented with microscopic hematuria and was identified with a hemizygous COL4A5 variant (NM033380.3: c.3374-3T > G) through whole-exome sequencing. Functional validation using a minigene splicing assay confirmed abnormal mRNA splicing leading to exon 38 skipping. This study identifies the variant c.3374-3T > G as a novel pathogenic non-canonical splice site mutation in the COL4A5 gene and expands the mutational spectrum of Alport syndrome.