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Abstract: SA-PO547

Diagnostic Utility of the Targeted Next-Generation Sequencing Panel Test for Suspicious Genetic Glomerular Diseases

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Kim, Ji Hye, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Lee, Hajeong, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background

A substantial proportion of glomerular diseases has genetic background, but there is no solid guideline concerning genetic work-up. The targeted next-generation sequencing (NGS) gene panel can identify possible mutations causing genetic glomerulopathies. We evaluated the diagnostic utility of targeted NGS panel for glomerular diseases.

Methods

Patients who received targeted NGS panel from 2017 to 2021 were included. Our NGS panel covered 23 variants causing genetic glomerulopathies including collagenopathies (COL4A3, COL4A4, COL4A5, and MYH9), genetic nephrotic syndrome (ACTN4, ADCK4, ANLN, COQ2, COQ6, EMP2, INF2, NPHS2, NUP107, PLCE1, and TRPC6), and other syndromic diseases (NPHS1, LAMB2, LCAT, LMX1B, PAX2, SMARCAL1, WDR73, and WT1). Variants were classified according to American College of Medical Genetics and Genomics 2015 guideline. Diagnostic yield was calculated as positivity rate of pathogenic or likely pathogenic variants.

Results

A total of 111 patients were included. The median age of disease onset and of receiving test was 9.0 [3.0;22.5] and 17.0 [7.5;33.0] years. Among them, 50 had family history of kidney disease and 3 had congenital anomalies. Seventy-three patients received percutaneous kidney biopsy for their pathologic diagnosis. Overall diagnostic yield of targeted NGS panel was 36% and higher in patients with younger onset age (<18 years) than those older [44.7% vs 17.1%, p=0.03]. It was associated with previous kidney biopsy (adjusted odds ratio (aOR), 6.23; 95% confidence interval (CI), 1.21-32.06), hematuria (aOR, 4.68; 95% CI, 1.32-16.56), systolic blood pressure (aOR, 0.94; 95% CI, 0.88-0.99) and absence of edema (aOR, 0.05; 95% CI, 0-0.66) even after covariate adjustment. Among 40 patients with positive gene test results, 16 changed their diagnosis from initial pathologic diagnosis and 13 patients received new genetic diagnosis.

Conclusion

Targeted NGS panel test for genetic glomerular diseases was useful in genetic diagnosis with a modest diagnostic yield of 36%. Previous kidney biopsy, hematuria, low systolic blood pressure and absence of edema were associated with higher positivity rate.