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Abstract: FR-PO656

DNASE1L3-Associated Nephropathy in Two Siblings Presenting C1q Nephropathy and Membranoproliferative Glomerulonephritis

Session Information

  • Pediatric Nephrology - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology


  • Kim, Dae Young, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Kang, Hee Gyung, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Ahn, Yo Han, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Deoxyribonucleases are in charge of extracellular DNA degradation, limiting inflammatory response. Deoxyribonuclease 1 like 3 (DNASE1L3) of DNase I family is known to be essential for the prevention of autoimmune disorders by sustaining plasma extracellular DNA homeostasis. Therefore, DNase1L3 gene mutation might cause autoimmune disorders, although only the cases of systemic lupus erythematous (SLE) had been reported previously. Here we report two siblings, sharing same compound heterozygote pathogenic variants of DNASE1L3, who were diagnosed with two different chronic glomerulonephritis.

Case Description

An eight-year-old boy presented hematuria with proteinuria and diagnosed as C1q nephropathy after kidney biopsy. Past medical history and family history were unremarkable. Despite treatment with immunosuppressive agents including steroid and tacrolimus, his kidney function deteriorated and lost at his age of 12. After living-donor kidney transplantation (KT), his allograft function has been well maintained until the last follow-up after 2 years of KT without proteinuria or any other extra-renal symptoms.

His brother also presented hematuria and proteinuria at his age of 6 and diagnosed as membranous nephropathy at his first kidney biopsy. Steroid and weekly rituximab treatment led to partial remission, but became resistant to immunosuppressant treatment. Follow-up biopsy revealed membranoproliferative glomerulonephritis type 2 and now he has been managed with medications including tacrolimus and mycophenolate. At his last follow-up on age of 13, his eGFR was 110mL/min/1.73m2 but nephrotic range proteinuria still persisted .

On multiple parallel sequencing, both siblings were found to have same compound heterozygote likely pathogenic variants of DNASE1L3, c.401_402dup and c.556A>G, which were inherited from their father and mother, respectively.


Here we report sibling cases of DNASE1L3 associated nephropathy, suggesting that dysfunction of deoxyribonucleases and predisposition to autoimmune diseases can be one of the pathogenic mechanisms of chronic glomerulonephritis. Interestingly, two siblings with same genetic predisposition showed different spectrum of nephropathies with distinct clinical courses, implying that there might be other modifying factors than the genetic predisposition.