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Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes

Despite the enormous economic and societal burden of chronic kidney disease (CKD), its pathogenesis remains elusive, impeding specific diagnosis and targeted therapy. Herein, we sought to elucidate the genetic causes of end-stage renal disease (ESRD) and identify genetic variants associated with CKD...

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Autores principales: Alaamery, Manal, Alghamdi, Jahad, Massadeh, Salam, Alsawaji, Mona, Aljawini, Nora, Albesher, Nour, Alghamdi, Bader, Almutairi, Mansour, Hejaili, Fayez, Alfadhel, Majid, Baz, Batoul, Almuzzaini, Bader, Almutairi, Adel F., Abdullah, Mubarak, Quintana, Francisco J., Sayyari, Abdullah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407681/
https://www.ncbi.nlm.nih.gov/pubmed/36035137
http://dx.doi.org/10.3389/fgene.2022.886038
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author Alaamery, Manal
Alghamdi, Jahad
Massadeh, Salam
Alsawaji, Mona
Aljawini, Nora
Albesher, Nour
Alghamdi, Bader
Almutairi, Mansour
Hejaili, Fayez
Alfadhel, Majid
Baz, Batoul
Almuzzaini, Bader
Almutairi, Adel F.
Abdullah, Mubarak
Quintana, Francisco J.
Sayyari, Abdullah
author_facet Alaamery, Manal
Alghamdi, Jahad
Massadeh, Salam
Alsawaji, Mona
Aljawini, Nora
Albesher, Nour
Alghamdi, Bader
Almutairi, Mansour
Hejaili, Fayez
Alfadhel, Majid
Baz, Batoul
Almuzzaini, Bader
Almutairi, Adel F.
Abdullah, Mubarak
Quintana, Francisco J.
Sayyari, Abdullah
author_sort Alaamery, Manal
collection PubMed
description Despite the enormous economic and societal burden of chronic kidney disease (CKD), its pathogenesis remains elusive, impeding specific diagnosis and targeted therapy. Herein, we sought to elucidate the genetic causes of end-stage renal disease (ESRD) and identify genetic variants associated with CKD and related traits in Saudi kidney disease patients. We applied a genetic testing approach using a targeted next-generation sequencing gene panel including 102 genes causative or associated with CKD. A total of 1,098 Saudi participants were recruited for the study, including 534 patients with ESRD and 564 healthy controls. The pre-validated NGS panel was utilized to screen for genetic variants, and then, statistical analysis was conducted to test for associations. The NGS panel revealed 7,225 variants in 102 sequenced genes. Cases had a significantly higher number of confirmed pathogenic variants as classified by the ClinVar database than controls (i.e., individuals with at least one allele of a confirmed pathogenic variant that is associated with CKD; 279 (0.52) vs. 258 (0.45); p-value = 0.03). A total of 13 genetic variants were found to be significantly associated with ESRD in PLCE1, CLCN5, ATP6V1B1, LAMB2, INVS, FRAS1, C5orf42, SLC12A3, COL4A6, SLC3A1, RET, WNK1, and BICC1, including four novel variants that were not previously reported in any other population. Furthermore, studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups.
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spelling pubmed-94076812022-08-26 Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes Alaamery, Manal Alghamdi, Jahad Massadeh, Salam Alsawaji, Mona Aljawini, Nora Albesher, Nour Alghamdi, Bader Almutairi, Mansour Hejaili, Fayez Alfadhel, Majid Baz, Batoul Almuzzaini, Bader Almutairi, Adel F. Abdullah, Mubarak Quintana, Francisco J. Sayyari, Abdullah Front Genet Genetics Despite the enormous economic and societal burden of chronic kidney disease (CKD), its pathogenesis remains elusive, impeding specific diagnosis and targeted therapy. Herein, we sought to elucidate the genetic causes of end-stage renal disease (ESRD) and identify genetic variants associated with CKD and related traits in Saudi kidney disease patients. We applied a genetic testing approach using a targeted next-generation sequencing gene panel including 102 genes causative or associated with CKD. A total of 1,098 Saudi participants were recruited for the study, including 534 patients with ESRD and 564 healthy controls. The pre-validated NGS panel was utilized to screen for genetic variants, and then, statistical analysis was conducted to test for associations. The NGS panel revealed 7,225 variants in 102 sequenced genes. Cases had a significantly higher number of confirmed pathogenic variants as classified by the ClinVar database than controls (i.e., individuals with at least one allele of a confirmed pathogenic variant that is associated with CKD; 279 (0.52) vs. 258 (0.45); p-value = 0.03). A total of 13 genetic variants were found to be significantly associated with ESRD in PLCE1, CLCN5, ATP6V1B1, LAMB2, INVS, FRAS1, C5orf42, SLC12A3, COL4A6, SLC3A1, RET, WNK1, and BICC1, including four novel variants that were not previously reported in any other population. Furthermore, studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9407681/ /pubmed/36035137 http://dx.doi.org/10.3389/fgene.2022.886038 Text en Copyright © 2022 Alaamery, Alghamdi, Massadeh, Alsawaji, Aljawini, Albesher, Alghamdi, Almutairi, Hejaili, Alfadhel, Baz, Almuzzaini, Almutairi, Abdullah, Quintana and Sayyari. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Alaamery, Manal
Alghamdi, Jahad
Massadeh, Salam
Alsawaji, Mona
Aljawini, Nora
Albesher, Nour
Alghamdi, Bader
Almutairi, Mansour
Hejaili, Fayez
Alfadhel, Majid
Baz, Batoul
Almuzzaini, Bader
Almutairi, Adel F.
Abdullah, Mubarak
Quintana, Francisco J.
Sayyari, Abdullah
Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
title Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
title_full Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
title_fullStr Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
title_full_unstemmed Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
title_short Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
title_sort analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407681/
https://www.ncbi.nlm.nih.gov/pubmed/36035137
http://dx.doi.org/10.3389/fgene.2022.886038
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