Thesis - Susan Murray (3).pdf (6.24 MB)
Download file

Utility of Gene Sequencing in Detecting Monogenic Disorders in Patients with Chronic Kidney Disease

Download (6.24 MB)
posted on 2022-03-10, 16:13 authored by Susan Murray
Chapter 1 provides an introduction to the topic and an overview of the currently known genetic causes of human chronic kidney disease.
Chapter 2 provides the details of the methods employed in this work.
Chapter 3 specifically discusses the effects of the General Data Protection Regulation (GDPR) and Health Research Regulation (HRR) on this research and the biobanked samples associated with it.
Chapter 4 details a retrospective analysis of individuals who had undergone genomic testing and kidney biopsy to assess if genomic testing gave any additional utility when compared to kidney biopsy alone and if genomic testing had the ability to potentially alter diagnosis or treatment. Of the 75 patients in 47 families who underwent kidney biopsy and genomics, 39 patients received a genetic diagnosis. A genetic diagnosis was much more likely to be made in those with a histological diagnosis of focal segmental glomerulosclerosis (FSGS) or Alport syndrome (59%) or tubulointerstitial kidney disease (TKD) (72%). Genetic testing could have potentially altered understanding of disease mechanism in 54% and could have altered treatment in 26% of cases.
Chapter 5 details a study in which patients who present for first time native kidney biopsy with suspected chronic kidney disease underwent genomic sequencing. We included all those over the age of 18 years who presented for kidney biopsy. We excluded those with a diagnosed of acute kidney injury, systemic lupus erythematosus of pauci-immune vasculitis. Patients underwent sequencing using a custom targeted next generation sequencing panel, which looked for variants in 227 genes known to cause kidney disease. We sequenced 50 patients. We detected pathogenic variants in two individuals (4%). Both patients had variants of significance were variants of COL4A4, which is associated with thin basement nephropathy and Alport syndrome. Additionally, one individual had a pathogenic variant in CFH. Though genotyping will identify inherited causes of disease in patients not known to have them, the detection rate remains low in a population that have not been suitably screened.
Chapter 6 details a study in which patients with end stage kidney disease, presenting for kidney biopsy underwent transplantation. We sequenced patients over the age of 18 who presented for kidney transplantation. We excluded those with pauci-immune vasculitis, systemic lupus erythematosus, drug-induced causes and those with renovascular kidney disease over the age of 50. Sequencing was performed using the same 227 gene panel. We sequenced 100 patients and detected variant in 22 patients (22%). Of those in whom we were able to detect a pathogenic variant 14 (14%) had a variant in PKD1 or PKD2, the genes most commonly responsible for autosomal dominant polycystic kidney disease.
Chapter 7 provides a final summary and conclusion.




First Supervisor

Prof. Peter J. Conlon

Second Supervisor

Prof. Gianpiero Cavalleri


Submitted for the Award of Doctor of Medicine to the Royal College of Surgeons in Ireland, 2021

Published Citation

Murray S,. Utility of Gene Sequencing in Detecting Monogenic Disorders in Patients with Chronic Kidney Disease [MD Thesis] Dublin: Royal College of Surgeons in Ireland; 2021

Degree Name

Doctor of Medicine (MD)

Date of award



  • Doctor of Medicine (MD)

Usage metrics