A Canonical Splice Site Variant in the Last Intron of the Col4a5 Gene Causing X-Linked Alport Syndrome in an Iranian Family: A Case Report Publisher



Abyar A ; Mohammadzadeh A ; Dehghanzad R ; Keramatipour M
Source: Journal of Advances in Medical and Biomedical Research Published:2025

Abstract

Alport syndrome (AS) is an inherited disorder of collagen type IV causing progressive renal disease, sensorineural hearing loss, and ocular abnormalities with variable severity. Here, we report a splice site variant in the COL4A5 gene, leading to X-linked Alport syndrome (XLAS) in two siblings from a non-consanguineous Iranian family. The proband was a 10-year-old boy with hematuria, proteinuria, and mild to moderate bilateral sensorineural hearing loss (BSNHL), who was diagnosed with AS based on renal pathology and genetic testing. Whole exome sequencing of the proband identified a hemizygous canonical splice site variant (c.4994+1G>A) in intron 52 of the COL4A5 gene. The same mutation was detected in his affected brother and heterozygous mother by Sanger sequencing, confirming the diagnosis of XLAS in the two affected individuals with renal impairment in this family. Our findings expand the geographic and mutational spectrum of COL4A5 splice site variants. To the best of our knowledge, this is the first reported c.4994+1G>A variant (ClinVar: rs2524654509) in an Iranian family, underscoring the need for including splice site analysis in diagnostic testing. Copyright © 2025,