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 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.886038

DOI=10.3389/fgene.2022.886038

ISSN=1664-8021

ABSTRACT=<p>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); <italic>p</italic>-value = 0.03). A total of 13 genetic variants were found to be significantly associated with ESRD in <italic>PLCE1</italic>, <italic>CLCN5</italic>, <italic>ATP6V1B1</italic>, <italic>LAMB2</italic>, <italic>INVS</italic>, <italic>FRAS1</italic>, <italic>C5orf42</italic>, <italic>SLC12A3</italic>, <italic>COL4A6</italic>, <italic>SLC3A1</italic>, <italic>RET</italic>, <italic>WNK1</italic>, and <italic>BICC1</italic>, 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.</p>