#5958 VALUE OF EXOME SEQUENCING “FIRST” FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common Mendelian diseases, that can progress to end-stage failure. Pathological variants in PKD1 or PKD2 genes are found about 78% 15% respectively. Additional such as GANAB, DNAJB11, ALG8/5 have been identified ADPKD. The sequencing by short read technics with exome capture Exome (ES) has describe technically challenging given 6 pseudogenes more than 98% homology exonic regions 1 33. Moreover, presence repeated motifs GC-rich PKD1/2 add difficulties. We study relevance “first-hand” during autosomal disease. Method ES was performed 684 unrelated adult patients from department Nephrology Sorbonne University, Paris, France. Genomic DNA extracted coding (37 megabases) were enriched Twist Human Core kit, paired-end sequenced on NextSeq500 (Illumina) machine. Sequences analyzed in-house SeqOne v1.3,2019 pipelines according GATK4 best practices. If necessary, co-segregation pathological studied Sanger relatives. Results Of patients, 143 had renal cysts. Pathogenic probably pathogenic variations PKD1, PKD2, DNAJB11 26 all cystic disease; respectively 17 3 DNAJB11. In this cohort, 18.2% reported 14 (82%) included exons All eventually confirmed without false positive. 5 diagnosed (19%), meaningful additional genetic data found, falling either CFTR, DHCR7, HFE, F8, ACTA2 gene. Conclusion highlights detection This strategy allowed us provide appropriate counseling (CFTR, DHCR7), management yet unexpected diseases affect ADPKD (F8, ACTA2) phenotype. Given these preliminary data, appears effective for PKD1/PKD2 variant detection, providing information 20% cases.