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Genetic Markers Among the Israeli Druze Minority Population With End-Stage Kidney Disease.
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.
Afiliação
  • Shlomovitz O; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed.
  • Atias-Varon D; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed.
  • Yagel D; Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
  • Barel O; Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel-Hashomer, Israel.
  • Shasha-Lavsky H; Azrieili Faculty of Medicine in Galilee, Bar-Ilan University, Safed, Israel; Department of Pediatric Nephrology, Galilee Medical Center, Nahariya, Israel.
  • Skorecki K; Azrieili Faculty of Medicine in Galilee, Bar-Ilan University, Safed, Israel.
  • Eliyahu A; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel.
  • Bathish Y; Nephrology Unit, Ziv Medical Center, Safed, Israel.
  • Frajewicki V; Institute of Nephrology and Hypertension, Carmel Medical Center, Haifa, Israel.
  • Kushnir D; Institute of Nephrology and Hypertension, Carmel Medical Center, Haifa, Israel.
  • Zaid R; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
  • Paperna T; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
  • Ofir A; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
  • Tchirkov M; Department of Nephrology and Hypertension, Rambam Health Care campus, Haifa, Israel.
  • Hassan K; Nephrology Unit, Galilee Medical Center, Nahariya, Israel.
  • Kruzel E; Nephrology Unit, Galilee Medical Center, Nahariya, Israel.
  • Khazim K; Nephrology Unit, Galilee Medical Center, Nahariya, Israel.
  • Geron R; Nephrology Unit, Galilee Medical Center, Nahariya, Israel.
  • Weisman I; Nephrology Unit, Galilee Medical Center, Nahariya, Israel.
  • Hanut A; Division of Nephrology and Hypertension Baruch Padeh Medical Center Poriya, Tiberias, Israel.
  • Nakhoul F; Division of Nephrology and Hypertension Baruch Padeh Medical Center Poriya, Tiberias, Israel.
  • Kenig-Kozlovsky Y; Department of Nephrology and Hypertension, Rambam Health Care campus, Haifa, Israel.
  • Refael G; Nephrology Unit, Mayanei HaYeshua Medical Center, Bnei Brak, Israel.
  • Antebi A; Institute of Nephrology and Hypertension, Carmel Medical Center, Haifa, Israel.
  • Storch S; Nephrology and Hypertension Unit, Bnai-Zion Medical Center, Haifa, Israel.
  • Leiba M; Dialysis Unit, Assuta Hospital, Haifa, Israel.
  • Kagan M; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed.
  • Shukrun R; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed.
  • Rechavi G; Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel-Hashomer, Israel; Azrieili Faculty of Medicine in Galilee, Bar-Ilan University, Safed, Israel.
  • Dekel B; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed; Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Has
  • Ben Moshe Y; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed.
  • Weiss K; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel; The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Assady S; Department of Nephrology and Hypertension, Rambam Health Care campus, Haifa, Israel; The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Vivante A; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Safed; Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israe
Am J Kidney Dis ; 83(2): 183-195, 2024 Feb.
Article em En | MEDLINE | ID: mdl-37717846
RATIONALE & OBJECTIVE: Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease (CKD). However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. This study characterized the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD). STUDY DESIGN: A national-multicenter cross-sectional study of Israeli Druze patients (an Arabic-speaking Near-Eastern transnational population isolate) who are receiving maintenance dialysis for ESKD. All study participants underwent exome sequencing. SETTING & PARTICIPANTS: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period. PREDICTORS: Demographics and clinical characteristics of kidney disease. OUTCOME: Genetic markers. ANALYTICAL APPROACH: Whole-exome sequencing and the relationship of markers to clinical phenotypes. RESULTS: 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 finding. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, and monogenic forms of noncommunicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in fewer than half of the participants. LIMITATIONS: This study was limited to Druze individuals, so its generalizability may be limited. CONCLUSIONS: Exome sequencing identified a genetic diagnosis in approximately 18% of Druze individuals 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. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) affects many people worldwide and has multiple genetic causes. However, there is limited information on the prevalence of genetic etiologies, especially among minority populations. Our national-multicenter study focused on Israeli Druze patients. Using exome-sequencing, we identified previously undetected genetic causes in nearly 20% of patients, including a new and population-specific WDR19 homozygous pathogenic variant. This mutation has not been previously described; it is extremely rare globally but is common among the Druze, which highlights the importance of studying minority populations with high rates of CKD. Our findings provide insights into the genetic basis of end-stage kidney disease in the Israeli Druze, expand the WDR19 phenotypic spectrum, and emphasize the potential value of genetic testing in such populations.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Insuficiência Renal Crônica / Falência Renal Crônica Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Humans País como assunto: Asia Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Insuficiência Renal Crônica / Falência Renal Crônica Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Humans País como assunto: Asia Idioma: En Ano de publicação: 2024 Tipo de documento: Article