Diagnostic Utility of Exome Sequencing Among Israeli Children With Kidney Failure.

Autor:	Ben-Moshe Y; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Shlomovitz O; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Atias-Varon D; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Genetic Kidney Disease Research Laboratory, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel., Haskin O; Nephrology Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Ben-Shalom E; Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Shasha Lavsky H; Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel.; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel., Volovelsky O; Pediatric Nephrology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Mane S; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA., Ben-Ruby D; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Genetic Kidney Disease Research Laboratory, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel., Chowers G; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Skorecki K; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel., Borovitz Y; Nephrology Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Kagan M; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Mor N; Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel., Khavkin Y; Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel., Tzvi-Behr S; Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Pollack S; Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel.; Technion Faculty of Medicine, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel., Toder MP; Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel.; Technion Faculty of Medicine, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel., Geylis M; Pediatric Nephrology Clinic, Soroka University Medical Center, Beer Sheva, Israel.; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel., Schnapp A; Pediatric Nephrology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Becker-Cohen R; Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Weissman I; Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel.; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel., Schreiber R; Pediatric Nephrology Clinic, Soroka University Medical Center, Beer Sheva, Israel.; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel., Davidovits M; Nephrology Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Frishberg Y; Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Magen D; Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel.; Technion Faculty of Medicine, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel., Barel O; Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Vivante A; Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.; Genetic Kidney Disease Research Laboratory, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.
Jazyk:	angličtina
Zdroj:	Kidney international reports [Kidney Int Rep] 2023 Jul 31; Vol. 8 (10), pp. 2126-2135. Date of Electronic Publication: 2023 Jul 31 (Print Publication: 2023).
DOI:	10.1016/j.ekir.2023.07.019
Abstrakt:	Introduction: Genetic etiologies are estimated to account for a large portion of chronic kidney diseases (CKD) in children. However, data are lacking regarding the true prevalence of monogenic etiologies stemming from an unselected population screen of children with advanced CKD. Methods: We conducted a national multicenter prospective study of all Israeli pediatric dialysis units to provide comprehensive "real-world" evidence for the genetic basis of childhood kidney failure in Israel. We performed exome sequencing and assessed the genetic diagnostic yield. Results: Between 2019 and 2022, we recruited approximately 88% ( n  = 79) of the children on dialysis from all 6 Israeli pediatric dialysis units. We identified genetic etiologies in 36 of 79 (45%) participants. The most common subgroup of diagnostic variants was in congenital anomalies of the kidney and urinary tract causing genes (e.g., EYA1 , HNF1B , PAX2 , COL4A1, and NFIA ) which together explain 28% of all monogenic etiologies. This was followed by mutations in genes causing renal cystic ciliopathies (e.g., NPHP1 , NPHP4 , PKHD1 , and BBS9 ), steroid-resistant nephrotic syndrome (e.g., LAGE3 , NPHS1 , NPHS2 , LMX1B , and SMARCAL1 ) and tubulopathies (e.g., CTNS and AQP2 ). The genetic diagnostic yield was higher among Arabs compared to Jewish individuals (55% vs. 29%) and in children from consanguineous compared to nonconsanguineous families (63% vs. 29%). In 5 participants (14%) with genetic diagnoses, the molecular diagnosis did not correspond with the pre-exome diagnosis. Genetic diagnosis has a potential influence on clinical management in 27 of 36 participants (75%). Conclusion: Exome sequencing in an unbiased Israeli nationwide dialysis-treated kidney failure pediatric cohort resulted in a genetic diagnostic yield of 45% and can often affect clinical decision making. (© 2023 International Society of Nephrology. Published by Elsevier Inc.)
Databáze:	MEDLINE
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