#4413 MOLECULAR SPECTRUM OF GENETIC ANOMALIES IN PEDIATRIC PATIENTS WITH EARLY ONSET OF RENAL CYSTIC DISEASE

Abstract Background and Aims Renal cystic disease (RCD) includes a spectrum of disorders with heterogenous clinical presentation. Among RCD are autosomal dominant polycystic kidney (ADPKD), recessive (ARPKD), ciliopathies, HNF1B-nephropathy, congenital anomalies the kidneys urinary tract (CAKUT). Diagnosis is based on criteria, yet, given extreme genetic heterogeneity phenotypic overlap among different conditions, confirmation by testing paramount for correct management recurrence risk assessment. Although genotype-phenotype correlations scanty, recently, coexisting variants in same gene or multiple cystogenes have been associated earlier more severe renal phenotype. The aim this study to describe molecular characteristics pediatric patients early onset provide correlations. Method A retrospective was conducted collecting prenatal early-childhood ultrasound finding hyper-echogenicity cysts. All were followed at Pediatric Nephrology Unit Città della Salute e Scienza University Hospital Torino, Italy. Genetic analyses mostly performed Immunogenetic Transplant Biology included exome sequencing (CES), array-CGH, MLPA single testing. Results 65 we recruited, 42 males (64.6%) 23 females (35.4%), mean age 8 ± 5.9 years (range 0-18). most frequent suspicion ADPKD (n = 40, 61.5%), CAKUT 9, 13.8%), ARPKD 8, 12.3%), ciliopathy tuberous sclerosis complex (TSC) 3, 4.6% each condition), medullary 2, 3.1%). Overall, causative (C4/C5) identified 39 (60.0%), 18 (27.7%) carriers uncertain significance (C3) (12.3%) inconclusive. 40 ADPKD, received conclusive diagnosis 20 (87%) PKD1, 2 (8.7%) PKD2, one HNF1B 14 carried C3 variants. and, notably, case observed biallelic PKD1. 21 PKD1 variants, 6 (28.6%) had (9.5%) an additional PKHD1 variant. TSC confirmed all 3 cases two them (66.7%) contiguous TSC2-PKD1 deletion. Two out BBS10, variant PKD2. Four (44.4%) solved (75%) PAX2 (25%), (22.2%) (33.3%) Causative de novo 10 (25.6%). Conclusion Our data confirms that evaluation powerful tool RCD, as witnessed detection rate 60%. majority cases, suspected whole deletion, highlighting need extensive analysis. Moreover, nine potentially contributing additive effect phenotype: patient BBS10 plus nonsense PKD2 In context, analysis CES permits simultaneous genes, uncovering both phenocopies. conclusion, driven characterization cysts allows avoid misdiagnosis, minimize diagnostic invasive investigations, set up follow-up, define risk, time- cost- efficient approach.