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Abstract: PO1336

Genetic Testing in Focal Segmental Glomerulosclerosis (FSGS): Tale of Three Stories

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Rajashekar, Gaurav, Washington University in St Louis, St Louis, Missouri, United States
  • Chen, Ying Maggie, Washington University in St Louis, St Louis, Missouri, United States

Group or Team Name

  • Washington University in St. Louis

Genetic testing in kidney disease has improved our understanding of various etiologies of glomerular diseases. FSGS is a histopathological diagnosis with diverse causes and patterns of inheritance. Genetic testing in FSGS has unlocked a treasure of pathogenic mutations that are either limited to the kidney or represent a broader extra-renal manifestation. Here we present 3 biopsy proven cases of FSGS with different genetic polymorphisms and varied presentations.

Case Description

Case 1: 29-year-old female with scoliosis, hearing loss, right optic nerve coloboma presented with 1.5 g/day of proteinuria and normal renal function when she was 16 years of age. Kidney biopsy revealed FSGS with 90% foot process effacement. 13 years later, her renal function worsened, with serum creatinine 1.4 mg/dl (baseline 0.9 mg/dl), and urine protein creatinine ratio of 4 g/g. Her mother had undergone a kidney transplant assumed to be secondary to reflux nephropathy. Genetic testing showed PAX2 truncated mutation c.430>T p.Gln 144* which can lead to FSGS, optic nerve coloboma and papillorenal syndrome.
Case 2: 21 year-old male with biopsy proven FSGS when he was 8 years old mentioned that his maternal grandfather suffered from unknown renal disease requiring dialysis and died in his 40’s. Genetic testing revealed hemizygous, truncating p.W58* variant in the CLCN5 gene. Variants in CLCN5 gene can cause Dent’s Disease manifesting later in life as proteinuria, nephrocalcinosis, hypercalciuria and renal failure. In addition he had variant of unknown significance NPHS1 designated p.T233A, and APOL1G2 risk allele predisposing him to develop FSGS.
Case 3: 21 year-old male, born with genital ambiguity, perineal hypospadias, 46 XY karyotype was noted to have 14 g of proteinuria, low albumin and hypertension. Kidney biopsy revealed FSGS, abnormal glomerular basement membrane. Genetic testing was positive for heterozygous intronic variant of WT-1 and heterozygous missense variant of SMARCAL1 p.R820H which are pathogenic variants that cause renal failure due to defective podocyte development and dysfunction respectively.


Genetic analysis for FSGS has become an important diagnostic tool in nephrology. We currently have over 50 genes that are known to be involved in FSGS. Reporting of different genetic variants and their occurrence is crucial to yield insight into our current understanding of FSGS.