MO045THE APPLICATION OF A NGS KIDNEY PANEL REVEALED KEY CHALLENGES OF PKD1-2 ANALYSIS: INTERPRETATION OF MISSENSE VARIANTS, SIGNIFICANCE OF VARIANTS IN DUPLICATED REGIONS AND HIGH ALLELIC HETEROGENEITY

Abstract Background and Aims Genetic testing has changed the clinical management of inherited kidney diseases patients, improving prognosis, surveillance therapy. On other hand, it put geneticists clinicians in front new challenges, as heterogeneity these disorders high number variants, with no clear genotype-phenotype correlation. Method 108 patients underwent genetic analysis through a focused NGS panel, named Nephroplex, containing 119 loci associated disorders. The study aimed to addressed landscape cystic individuals analyze PKD1 PKD2 variants non-cystic individuals. Results Following diagnostic criteria, were divided (n=36) (n=72). Among group causative mutation was detected 51% cases. We found thirty-seven 26 out 35 In particular, 12 shown be damaging nine that reported public database, CLINVAR Mayo Clinic databases. pathogenic twelve truncating remaining missense variants. Of note, 7 mutations located duplicated regions. Moreover, three we (i) frameshift hemizygote OFD1 (ii) compound heterozygote PKHD1 (iii) MUC1 variant, framing diagnosis oro-facio-digital type 1, autosomal recessive polycystic disease dominant tubulointerstitial disease, respectively. Interestingly, 28 PKD1-2 rare 21 75 adult non (28%). most observed genes (82% vs 18% PKD2). Eighteen described literature likely benign or uncertain significance, while 10 novel silico revealed exon 15. great part variations reside into Conclusion Our data showed ADPKD retains unique given degree homology his pseudogenes allelic