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Abstract: TH-PO986

Rapid Genome Sequencing to Guide Clinical Decision Making in FSGS

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Marasa, Maddalena, Columbia University Medical Center, New York, New York, United States
  • Ahram, Dina, Columbia University Medical Center, New York, New York, United States
  • Rehman, Atteeq U., New York Genome Center, New York, New York, United States
  • Mitrotti, Adele, Columbia University Medical Center, New York, New York, United States
  • Jain, Namrata Gargee, Columbia University Medical Center, New York, New York, United States
  • Weng, Patricia L., UCLA, Los Angeles, California, United States
  • Piva, Stacy E., Columbia University Medical Center, New York, New York, United States
  • Kil, Byum hee, Columbia University Medical Center, New York, New York, United States
  • Fernandez, Hilda E., Columbia University Medical Center, New York, New York, United States
  • Uy, Natalie S., Columbia University Medical Center, New York, New York, United States
  • Chatterjee, Debanjana, Columbia University Medical Center, New York, New York, United States
  • Radhakrishnan, Jai, Columbia University Medical Center, New York, New York, United States
  • Appel, Gerald B., Columbia University Medical Center, New York, New York, United States
  • Santoriello, Dominick, Columbia University Medical Center, New York, New York, United States
  • Bomback, Andrew S., Columbia University Medical Center, New York, New York, United States
  • Lin, Fangming, Columbia University Medical Center, New York, New York, United States
  • D'Agati, Vivette D., Columbia University Medical Center, New York, New York, United States
  • Jobanputra, Vaidehi, New York Genome Center, New York, New York, United States
  • Sanna-Cherchi, Simone, Columbia University Medical Center, New York, New York, United States
Background

About 30% of children with focal segmental glomerulosclerosis (FSGS) have a genetic cause. While genetic forms are usually resistant to immunosuppressants, steroids are still the first-line treatment regardless of individual genetic make-up. We hypothesized that rapid whole genome sequencing (WGS) at diagnosis will help guide clinical management by a) improving diagnosis, b) sparing immunosuppressive treatment in cases with Mendelian mutations, c) identifying cases responsive to targeted therapy, d) improving counseling for both renal and extrarenal disease, and e) improving transplant evaluation and outcome.

Methods

We conducted CLIA-certified rapid WGS to guide decision-making in 10 children and young adults affected by biopsy-proven FSGS where a genetic diagnosis could affect therapeutic decision. Return of results (ROR) included therapeutic, familial and pre-transplant counseling.

Results

Turn-around time from consent to ROR averaged 20 days (15-42). WGS identified a diagnostic genotype in 5/10 patients and prompted biopsy revision in 2 cases leading to management change in virtually all cases, including holding/stopping immunosuppression in 6/10 cases, new treatment in 5/10 cases and improved transplant evaluation in 2 cases (Fig. 1). Genetic diagnosis also prompted early screening for subclinical neurological disease in a patient.

Conclusion

Rapid WGS in FSGS can improve medical management and possibly outcome by sparing ineffective and toxic treatment, identifying forms amenable to etiologic treatment, and inform familial counseling and pre-transplant evaluation thus optimizing organ allocation.

Funding

  • Other NIH Support