#2684 DIAGNOSTIC YIELD OF A TARGETED GENE PANEL FOR MONOGENIC KIDNEY DISEASES: A EUROPEAN STUDY

Abstract Background and Aims Despite advances in understanding the underlying causes of CKD, 20% cases remain unexplained (1). A genomic approach has potential to identify cause CKD a significant portion pediatric adult patients, with estimated diagnostic rates 5-30% (2). However, there is lack consensus scientific community on best algorithm. The DECIDE project (Diagnostic EffiCacy kIdney Disease European) European collaboration that aims address this issue by evaluating rate targeted gene panel large cohort patients. Method involved three Italian two Spanish centers, encompassing both study used Nephropathies Solution Panel (NES, SOPHiA Genetics), which covers 44 kidney-related genes, test patients high suspicion genetic kidney disease. clinical presentation was classified into cystic disease, glomerulopathy, CAKUT, tubulopathy, nephrocalcinosis, other, negative phenotype. yield NES calculated. To assess genotype-phenotype relationship, Kaplan-Meier analyses were performed. Additionally, results obtained from alternative technologies, such as larger panels, WES hybridization arrays, results, also collected. Results As far now collected 632 data. evaluate accuracy panel, number (likely) pathogenic variants correlated phenotype analyzed. shown Figure 1, 46% for 41% 33% tubulopathies, 28% 14% 2% (in context segregation or cascade test) 8% other. Table 1 shows main genes diagnosis PKD1, PKD2, COL4A3, COL4A4, COL4A5. In affected mean age failure 48 years presence variants, 59 VUS, no events reported tests. curve confirmed worse prognosis (p-value<0.05). correlation terms time replacement therapy observed glomerulopathic non-diagnostic 21 further investigations An enriched disease didn't detect any while only one patient diagnosed using WES. Hybridization Array identified deletion under investigation may be related (Nephronophthisis). Conclusion preliminary project, based about 600 data, demonstrate showed good (46%) glomerulopathy (41%), but it appears less effective other presentations. average comparable published data approaches. additional tests WES, CGH-array found limited usefulness, they variant. These suggest new approaches are necessary uncover hidden components rare renal conditions.