Whole exome sequencing in pediatric patients with glomerulonephritis

Marina Perić^1*Marija Branković²Natasa Stajic¹Jovana Putnik^1,3Aleksandra Paripovic^1,3Milena Jankovic⁴Dejan Nikolic^2,3Filip Milanovic^2,3Ivana Novakovic³Vladislav Vukomanovic^1,3

• ¹The Institute for Health Protection of Mother and Child Serbia, Belgrade, Serbia
• ²University Children's Hospital, Belgrade, Belgrade, Serbia
• ³Faculty of Medicine, University of Belgrade, Belgrade, Serbia
• ⁴Neurology Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia

Introduction: High throughput sequencing methods revealed disease-causing and susceptibility genes underlying glomerulonepehritis (GNs). Besides this, genetic disorders mimicking GNs may be diagnosed in this way. The aim of this study was to perform whole exome sequencing (WES) in a cohort of sporadic pediatric patients diagnosed with the primary or secondary GN. Method: Thirty-one patients with GN were genetically analyzed and 50 nephrologically and immunologically healthy pediatric patients (control group - CG). Allele frequencies were compared with the GnomAD database. WES was performed in the laboratory 3billion in South Korea. Results: Among 10 patients with primary GN, two patients were positive on WES (20%) - one had likely pathogenic heterozygous variant in the COL4A3 gene associated with Alport syndrome, and one had a heterozygous novel variant of uncertain significance in CD46 gene associated with atypical hemolytic uremic syndrome (aHUS). In two of 14 patients with SLE and GN a heterozygous pathogenic variant (c.841_849+19del) in the C2 gene was detected. We found no significant variants in seven patients with HSP and GN. Conclusion: WES helped us to detect hereditary diseases that have a clinical presentation like GN, including Alport syndrome and possible aHUS. Also, finding susceptibility genes in GNs helped us to understand disease pathophysiology.