Introduction: Monogenic disorders account for up to 9.3% of all-cause chronic kidney disease (CKD). Among these, Collagen type IV-alpha-associated nephropathies (COL4A-AN) stand out as the second most common form. COL4A-AN is a hereditary nephritis caused by mutations in COL4A3, COL4A4 or COL4A5 encoding the type IV collagen α3, α4, and α5 chains. The clinical spectrum of COL4A-AN diseases varies widely, including severe form like alport syndrome to less severe form such as thin basement disease. No specific therapy exists yet.
Methods: We started the collagen type IV mutation Screening Program in patients who initiated renal replacement therapy before reaching 50 years old on chronic dialysis and post-kidney transplantation (KTx) in this hospital. We conducted whole exome sequencing with targeting 6 monogenic genes associated with renal diseases, including PKD1, PKD2, COL4A3, COL4A4, COL4A5, and UMOD.
Results: We have conducted DNA sequencing on 152 blood samples and identified four patients diagnosed with COL4A-AN until end of 2023.  Interestingly, we confirmed a family cluster (two sons and their mother) of IgA nephropathy and Alport syndrome. The indicated brothers were diagnosed as IgAN by renal biopsy at their age 8 and 10 with presentation of hematuria and proteinuria. They received kidney transplantation with triple therapy for more than 15 years. The whole exome sequencing (WES) demonstrated COL4A5 c.2917+ 1 del. Our result showed COL4A-AN is the most common monogenic disease in chronic kidney disease in our hospital. 
Conclusions: Modern genetics has enabled us to recognize the compounding role of type IV collagen mutations in the pathogenesis of other causes of CKD. Although there is a huge phenotypic heterogeneity of Alport syndrome, our results showed COL4A-AN accounting for a significant portion of CKD.