Abstract: SA-PO404
Diagnostic Utility of Next-Generation Sequencing in Patients Presenting for Percutaneous Renal Biopsy
Session Information
- Genetic Diseases of the Kidney - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Murray, Susan Louise, Beaumont Hospital, Dublin, Ireland
- Benson, Katherine A., Royal College of Surgeons in Ireland, Dublin, Ireland
- Doyle, Ross P., Mater Misericordiae University Hospital, Dublin, Ireland
- Cavalleri, Gianpiero, RCSI, Dublin, Italy
- Godson, Catherine, The Conway Institute of Biomolecular and Biomedical, Belfield, Dublin, Wilton, Ireland
- Conlon, Peter J., Beaumont Hospital, Dublin 9, Co Dublin, Ireland
Background
Genetic testing is fast becoming a first line of investigation in many branches of medicine. Genetic causes of kidney disease may be under-recognised and exome sequencing has been shown to detect pathogenic mutations in up to 10% of patients with CKD. We aimed to genotype a cohort of patients undergoing renal biopsy.
Methods
We recruited adult patients attending for percutaneous kidney biopsy under investigation for acute or chronic kidney disease, over an eight-year period from 2010 to 2018. Patients undergoing post-transplant renal biopsy or patients whose renal biopsy showed diabetic nephropathy or pauci-immune vasculitis were excluded. Patients underwent next generation sequencing using a specially designed Roche NimbleGen HeatSeq panel, which sequenced for 227 genes associated with kidney disease. Data was analysed using an in-house bioinformatics pipeline and variants were classified using gold-standard American College of Medical Genetics and Genomics guidelines for variant pathogenicity.
Results
We sequenced 69 patients who had undergone native renal biopsy. These included 21 patients with a histological diagnosis of IgA nephropathy, 19 with other forms of glomerular disease, 14 with interstitial nephritis, and 15 with non-specific changes on histology. We identified a pathogenic variant for Alport Syndrome (COL4A4) in a single patient (1.5%). We also identified a variant of unknown significance in CFH in the same patient, which may be contributing to the patient’s low complement levels. Additionally, we identified noteworthy variants of unknown significance in 39 patients including 12 loss-of-function variants and three truncating variants in genes previously established as contributing to renal disease.
Conclusion
Next generation sequencing may be a useful addition to renal biopsy in certain groups of patients. In an undifferentiated group of patients undergoing renal biopsy, we detected pathogenic mutations in 1.5%. This diagnostic yield may be improved when DNA is available from parents and other affected family members and with careful selection of patients sent for testing.
Funding
- Private Foundation Support