Genetic Markers Among the Israeli Druze Minority Population With End-Stage Kidney Disease

• Published in: American journal of kidney diseases Vol. 83; no. 2; p. 183
• Main Authors: Shlomovitz, Omer, Atias-Varon, Danit, Yagel, Dina, Barel, Ortal, Shasha-Lavsky, Hadas, Skorecki, Karl, Eliyahu, Aviva, Bathish, Younes, Frajewicki, Victor, Kushnir, Daniel, Zaid, Rinat, Paperna, Tamar, Ofir, Ayala, Tchirkov, Marina, Hassan, Kamal, Kruzel, Etty, Khazim, Khaled, Geron, Ronit, Weisman, Irit, Hanut, Anaam, Nakhoul, Farid, Kenig-Kozlovsky, Yael, Refael, Gery, Antebi, Alon, Storch, Shimon, Leiba, Marcel, Kagan, Maayan, Shukrun, Rachel, Rechavi, Gidi, Dekel, Benjamin, Ben Moshe, Yishay, Weiss, Karin, Assady, Suheir, Vivante, Asaf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2024
• Subjects: Adult; Ciliopathy; CKD; Cross-Sectional Studies; Druze; ESKD; Exome Sequencing; Genetic; Genetic Markers; Health Disparate Minority and Vulnerable Populations; Humans; Israel - epidemiology; Kidney Failure, Chronic - epidemiology; Kidney Failure, Chronic - genetics; Kidney Failure, Chronic - therapy; Minority; Minority Groups; Monogenic; Nephronophtisis-13; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - genetics; WDR19; Israel; Druze; Ciliopathy; Nephronophtisis-13; Exome Sequencing; Minority; ESKD; WDR19; Genetic; CKD; Monogenic; genetic; exome sequencing; nephronophtisis-13; minority; monogenic
• ISSN: 0272-6386; 1523-6838; 1523-6838
• DOI: 10.1053/j.ajkd.2023.06.006

Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease. However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. The objective of this study was to characterize the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD). A national-multicenter cross-sectional study of Israeli Druze patients receiving maintenance dialysis for ESKD. an Arabic-speaking Near-Eastern transnational population isolate. All study participants underwent exome sequencing. & Participants: We recruited 94 adults with ESKD, which comprised 97% of the total 97 dialysis-treated Druze individuals throughout Israel during the study period. Demographics and clinical characteristics of kidney disease Genetic markers. Whole exome sequencing and their relationship of markers to clinical phenotypes. We identified genetic etiologies in 17 of 94 participants (18%). None had a previous molecular diagnosis. A novel, population-specific, WDR19 homozygous pathogenic variant (p.Cys293Tyr) was the most common genetic diagnosis. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, as well as monogenic forms of non-communicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in less than half of the participants. This study was limited to Druze, so its generalizability may be limited. Exome sequencing identified a genetic diagnosis in approximately 18% of in Druze with ESKD. These results support conducting genetic analyses in minority populations with high rates of CKD and for whom phenotypic disease specificity may be low.