Kidney Week

Abstract: FR-OR070

Nationwide Diagnostic Yield of Clinical Genomics in Patients with Suspected Genetic Kidney Disease

Session Information

• Genetic Diseases and the Kidneys
  November 08, 2019 | Location: 144, Walter E. Washington Convention Center
  Abstract Time: 06:18 PM - 06:30 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Mallett, Andrew John, Royal Brisbane and Women's Hospital, Stafford, Queensland, Australia

Andrew John Mallett, MBBS, PhD, FASN



A/Prof Andrew Mallett is a Nephrologist with a special interest in inherited kidney disease. A/Prof Mallett is a Consultant Nephrologist at RBWH and co-lead of the Queensland Conjoint Renal Genetics Service having undertaken a Churchill Fellowship and PhD in nephrogenetics. He is the National Director of the KidGen Collaborative, the AGHA Renal Genetics and HIDDEN Flagships, and is RBWH Clinical Council Co-Chair. In 2019 A/Prof Mallett was awarded the MNHHS “Rising Star” Research Excellence and UQ Distinguished Young Alumnus Awards.

• Jayasinghe, Kushani C., Monash Health, Clayton, New South Wales, Australia

Kushani C. Jayasinghe,

• Quinlan, Catherine, The Royal Children's Hospital, Melbourne, Victoria, Australia

Catherine Quinlan,

Group or Team Name

• Australian and Melbourne Genomics Renal Genetics Flagships part of the KidGen collaborative

Background

With increased understanding of genetic kidney disease (GKD), genomic testing is translating from research to clinic. Rigorous evaluation of clinical practice and patient outcomes is required to guide value-based healthcare. We aimed to describe diagnostic outcomes of clinically accredited genomic testing delivered by nationwide multidisciplinary team (MDT) clinics for patients with suspected GKD.

Methods

Sequential incident patients undergoing clinically indicated genomic testing for presumed GKD from 18 Australian MDT clinics 2016-19 were analysed (HREC/16/MH/251). A molecular diagnosis constituted clinical reporting of pathogenic and/or likely pathogenic variant/s in gene/s associated with the patient kidney phenotype with concordant inheritance. All genomic testing included restriction of variant analysis to a phenotype-derived gene list. Full author list online at KidGen.org.au

Results

Of 824 patients, 52.1% were female. Median age was 26 years. A molecular diagnosis was made in 43.7%. A further 15.4% had a variant/s of uncertain significance (VUS), of which 23.6% were clinically compelling but require further functional validation or additional segregation.
The diagnostic yield for whole genome (WGS n=92, 41.3%), whole exome (WES n=231, 40.7%) and clinical exome (CES n=392, 42.3%) sequencing was similar (p=0.91). Median age at test request for WGS (42yrs) was significantly older (p<0.00001) than WES (27yrs) and CES (18yrs). Of all patients with a genetic finding, 53.6% involved variation in 7 genes (COL4A3, COL4A4, COL4A5, PKD1, PKD2, PKHD1, HNF1B). Stratifying by age at test request, the diagnostic rate was not significantly different between 0-15yrs (41.8%), 16-25yrs (48.5%) and 26+yrs (44.2%) (p=0.25). The gender mix in these age groups was significantly different (female 45.8% vs 51.5% vs 56.7%, p=0.015).

Conclusion

Clinical genomics delivered by MDT clinics are diagnostically effective for suspected GKD. Neither sequencing approach nor age group at test request appear to impact diagnostic yield though WGS patients in this cohort were older and gender mix changed with increasing patient group age. Clinical utility studies are required to clarify impact of these diagnostic outcomes.

Funding

• Government Support - Non-U.S.