دورية أكاديمية
Diagnostic Yield and Benefits of Whole Exome Sequencing in CAKUT Patients Diagnosed in the First Thousand Days of Life
| العنوان: | Diagnostic Yield and Benefits of Whole Exome Sequencing in CAKUT Patients Diagnosed in the First Thousand Days of Life |
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| المؤلفون: | Werfel, Lina, Martens, Helge, Hennies, Imke, Gjerstad, Ann Christin, Fröde, Kerstin, altarescu, gheona, Valenzuela, Irene |
| المساهمون: | Institut Català de la Salut, Werfel L Department of Human Genetics, Hannover Medical School, Hannover, Germany. Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. Martens H Department of Human Genetics, Hannover Medical School, Hannover, Germany. Hennies I, Fröde K Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. Gjerstad AC Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. Altarescu G Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. Valenzuela Palafoll I Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Anomalies cromosòmiques, Infants, Ronyons - Malalties - Diagnòstic, Aparell genitourinari - Malaties - Diagnòstic, DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Urogenital Abnormalities, DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronic::Kidney Failure, Chronic, NAMED GROUPS::Persons::Age Groups::Infant, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation, ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::anomalías urogenitales, ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::insuficiencia renal crónica::fallo renal crónico, DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::lactante, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación |
| الوصف: | Infancy; Reverse phenotyping; Whole exome sequencing ; Infancia; Fenotipado inverso; Secuenciación del exoma completo ; Infància; Fenotipat invers; Seqüenciació de l'exoma complet ; Introduction Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause of chronic kidney disease (CKD) and the need for kidney replacement therapy (KRT) in children. Although more than 60 genes are known to cause CAKUT if mutated, genetic etiology is detected, on average, in only 16% of unselected CAKUT cases, making genetic testing unproductive. Methods Whole exome sequencing (WES) was performed in 100 patients with CAKUT diagnosed in the first 1000 days of life with CKD stages 1 to 5D/T. Variants in 58 established CAKUT-associated genes were extracted, classified according to the American College of Medical Genetics and Genomics guidelines, and their translational value was assessed. Results In 25% of these mostly sporadic patients with CAKUT, a rare likely pathogenic or pathogenic variant was identified in 1 or 2 of 15 CAKUT-associated genes, including GATA3, HNF1B, LIFR, PAX2, SALL1, and TBC1D1. Of the 27 variants detected, 52% were loss-of-function and 18.5% de novo variants. The diagnostic yield was significantly higher in patients requiring KRT before 3 years of age (43%, odds ratio 2.95) and in patients with extrarenal features (41%, odds ratio 3.5) compared with patients lacking these criteria. Considering that all affected genes were previously associated with extrarenal complications, including treatable conditions, such as diabetes, hyperuricemia, hypomagnesemia, and hypoparathyroidism, the genetic diagnosis allowed preventive measures and/or early treatment in 25% of patients. Conclusion WES offers significant advantages for the diagnosis and management of patients with CAKUT diagnosed before 3 years of age, especially in patients who require KRT or have extrarenal anomalies. ; This work was supported by grants from the Else Kröner-Fresenius-Stiftung (2018_Kolleg.12, Clinician Scientist ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2468-0249 |
| العلاقة: | Kidney International Reports;8(11); https://doi.org/10.1016/j.ekir.2023.08.008Test; Werfel L, Martens H, Hennies I, Gjerstad AC, Fröde K, Altarescu G, et al. Diagnostic Yield and Benefits of Whole Exome Sequencing in CAKUT Patients Diagnosed in the First Thousand Days of Life. Kidney Int Reports. 2023 Nov;8(11):2439–57.; https://hdl.handle.net/11351/10741Test; 001109004400001 |
| DOI: | 10.1016/j.ekir.2023.08.008 |
| الإتاحة: | https://doi.org/10.1016/j.ekir.2023.08.008Test https://hdl.handle.net/11351/10741Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9BF4344E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24680249 |
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| DOI: | 10.1016/j.ekir.2023.08.008 |