P0059CLINICAL AND IMAGING FEATURES OF A NOVEL DNAJB11 MUTATION COMPARED TO PKD1-PKD2 ADULT POLYCYSTIC KIDNEY DISEASE (ADPKD). TWO DIFFERENT DISEASES?

Abstract Background and Aims ADPKD is characterized by the progressive development of bulky renal cysts, often resulting in end-stage renal disease (ESRD). Among this group 85% of cases recognize a genetic mutation concerning PKD1/PKD2 genes (ADPKD). Among the remaining 15% of ADPKD patients, DNAJB11 mutations (DNAJB11-PKD) has been recently recognized. [Cornec-Le Gall E, Olson RJ, Beesse W t al. Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease. Am Journ Hum Gen 2018, 102:832-844.] DNAJB11 encodes a co-chaperone of the endoplasmic reticulum (ER) also called ERdj3. It is part of the HSP40 protein family and plays a central role in both intracellular and extracellular proteomic homeostasis (proteostasis). In the intracellular compartment it acts as a co-chaperone in the pathway of the unfolded protein response (UPR) in which it binds misfolded proteins which have to be secreted and activates BiP an HSP70 of ER whose function is to correct the misfolding. In our Nephrology Unit we collected the largest cohort of patients with a new stop codon mutation (p.Arg34*) of DNAJB11. All patients are relatives of different ranks and were born in a small village in the mountains of the Parma province.In this study we compare clinical features of DNAJB11-PKD with ADPKD to define differences between the two groups. Method We identified retrospectively from outpatient and dialysis databases of the Nephrology Unit of Parma patients carrying pArg34* DNAJB11 or PKD1-PKD2 mutations. We collected the clinical features and the available diagnostic imaging of all identified patients. Results We collected 19 patients with DNAJB11-PKD and 37 with ADPKD. The clinical characteristics are reported in Figure 1 . Our DNAJB11-PKD cohort vs ADPKD presented significantly a normal renal size (median value 10.5cm vs 16cm respectively) and smaller cysts size (median value 2cm vs 5cm respectively). Interestingly 5/19 DNAJB11 patients had type 2 diabetes vs no cases in the ADPKD group (p