K JAYASINGHE1,2,3, Z STARK3,4,8, P KERR1,2, A MALLETT3,6,8, C QUINLAN3,7, MELBOURNE GENOMICS HEALTH ALLIANCE5
1Monash Health, Clayton, Australia, 2Monash University, Clayton, Australia, 3Murdoch Children’s Research Institute, Parkville, Australia, 4Victorian Clinical Genetics Services, , Parkville, Australia, 5Melbourne Genomics Health Alliance, , Australia, 6Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia, 7Department of Paediatric Nephrology, Royal Children’s Hospital, Parkville, Australia, 8KidGen Collaborative, Australian Genomics Health Alliance, , Australia
Aim: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected GKD.
Background: Genetic kidney disease (GKD) is increasingly recognized as an important cause of CKD and can be difficult to accurately diagnose using traditional diagnostic strategies. There is a paucity of data on the clinical utility of genomic testing in kidney disease patients.
Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia.
Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p<0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis following ES. A diagnosis on ES was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%) and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%).
Conclusions: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.
Dr Kushani Jayasinghe is an adult nephrologist based at Monash Health with an interest in genetic kidney disease. Her PhD studies through Monash University focuses on the clinical utility and feasibility of genomic sequencing in patients with suspected genetic kidney disease.