Genetic testing in focal segmental glomerulosclerosis: to whom and when?

Abstract Background Genetic causes are increasingly recognized in patients with Focal Segmental Glomerulosclerosis (FSGS), but it remains unclear which should undergo a genetic study. Our objective was to determine the frequency and distribution of variants steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) or undetermined cause (FSGS-UC). Methods We performed targeted exome sequencing 84 genes associated glomerulopathy adult-onset SRNS-FSGS FSGS-UC after ruling out secondary causes. Results 76 met study criteria, 24 presented SRNS 52 FSGS-UC. detected FSGS-related disease-causing 27/76 (35.5%). There were no differences between non-genetic age, proteinuria, GFR, serum albumin, BMI, hypertension, diabetes, family history. Hematuria more prevalent among found 19 pathogenic COL4A3-5 16 (29.3%) patients. NPHS2 mutations identified 6 (16.2%) The remaining cases had affecting INF2, OCRL, ACTN4 APOL1 high-risk alleles. common than (41.7% vs 32.7%). Four (40%) variants. COL4A most finding patients, twelve (76.4%) carrying these genes. Conclusions substantial number FSGS-UC, regardless age onset disease patient's In our experience, testing be routine clinical practice for diagnosis this group