A Deeper Insight into COL4A3, COL4A4, and COL4A5 Variants and Genotype-Phenotype Correlation of a Turkish Cohort with Alport Syndrome

Abstract

Introduction: Alport syndrome (AS) is an inherited, rare, progressive kidney disease that affects the eye and ear physiology. Pathogenic variants of COL4A5 account for 85% of all cases, while COL4A3 and COL4A4 account for the remaining 15%. Methods: Targeted next-generation sequencing of the COL4A3, COL4A4, and COL4A5 genes was performed in 125 Turkish patients with AS. The patients were compared to 45 controls and open-access population data. Results: The incidence of AS variants in patients was found as 21.6%. 27 variants were identified as pathogenic/likely pathogenic, 28 as variant of uncertain significance, and 52 as benign/likely benign. We also found 31 novel variants (14 in COL4A3, 6 in COL4A4, and 11 in COL4A5) of which 27 were classified as pathogenic/likely pathogenic. Pathogenic/likely Pathogenic variants were most commonly found in the COL4A5 gene, consistent with the literature. This study contributed novel variants associated with AS to the literature. Conclusion: Genetic testing is a crucial part for the diagnosis and management of AS. Studies on the genetic etiology of AS are limited for the Turkish population. We believe that this study will contribute to the literature and the clinical decision-making process of patients with AS and emphasize the importance of genetic counseling.(c) 2023