Abstract：
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).
METHODS: 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.
METHODS: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period.
METHODS: Demographics and clinical characteristics of kidney disease.
RESULTS: Genetic markers.
METHODS: 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.
CONCLUSIONS: 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.
UNASSIGNED: 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.
METHODS: 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.
METHODS: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period.
METHODS: Demographics and clinical characteristics of kidney disease.
RESULTS: Genetic markers.
METHODS: 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.
CONCLUSIONS: 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.
UNASSIGNED: 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.
摘要：
目的：在约10%的慢性肾脏病成人中发现了遗传病因。然而,缺乏有关单基因病因患病率的数据，尤其是在少数群体中。这项研究的目的是表征患有终末期肾脏疾病（ESKD）的以色列少数民族成员之间的遗传标记。
方法：一项针对以色列德鲁兹患者接受ESKD维持性透析的国家多中心横断面研究。讲阿拉伯语的近东跨国人口孤立。所有研究参与者都进行了外显子组测序。
方法：&参与者：我们招募了94名患有ESKD的成年人，在研究期间，占整个以色列97名接受透析治疗的德鲁兹人的97％。
方法：肾脏疾病结局的人口统计学和临床特征：遗传标记。
方法：全外显子组测序及其标记与临床表型的关系。
结果：我们在94名参与者中的17名（18％）中确定了遗传病因。没有人以前有分子诊断。一部小说,特定人群，WDR19纯合致病变异体(p。Cys293Tyr）是最常见的遗传诊断。其他单基因病因包括PKD1，PKD2，IV型胶原突变，以及非传染性疾病的单基因形式。在不到一半的参与者中，外显子组前的临床诊断与最终的分子诊断相对应。
结论：这项研究仅限于德鲁兹，所以它的普适性可能是有限的。
结论：外显子组测序确定了大约18％的具有ESKD的德鲁兹患者的遗传诊断。这些结果支持在CKD高发且表型疾病特异性可能较低的少数民族人群中进行遗传分析。
方法：一项针对以色列德鲁兹患者接受ESKD维持性透析的国家多中心横断面研究。讲阿拉伯语的近东跨国人口孤立。所有研究参与者都进行了外显子组测序。
方法：&参与者：我们招募了94名患有ESKD的成年人，在研究期间，占整个以色列97名接受透析治疗的德鲁兹人的97％。
方法：肾脏疾病结局的人口统计学和临床特征：遗传标记。
方法：全外显子组测序及其标记与临床表型的关系。
结果：我们在94名参与者中的17名（18％）中确定了遗传病因。没有人以前有分子诊断。一部小说,特定人群，WDR19纯合致病变异体(p。Cys293Tyr）是最常见的遗传诊断。其他单基因病因包括PKD1，PKD2，IV型胶原突变，以及非传染性疾病的单基因形式。在不到一半的参与者中，外显子组前的临床诊断与最终的分子诊断相对应。
结论：这项研究仅限于德鲁兹，所以它的普适性可能是有限的。
结论：外显子组测序确定了大约18％的具有ESKD的德鲁兹患者的遗传诊断。这些结果支持在CKD高发且表型疾病特异性可能较低的少数民族人群中进行遗传分析。
