HJ MCCARTHY1,2,3, AJ MALLETT3,4, G HO3,5, K HOLMAN3,5, E FARNSWORTH3,5, C PATEL3,6, JT FLETCHER3,7, A MALLAWAARACHCHI3,8, C QUINLAN3,9, B BENNETTS2,3,5, SI ALEXANDER1,2,3
1Department of Nephrology, Children’s Hospital at Westmead, Westmead, Australia, 2University of Sydney, Sydney, Australia, 3KIDGEN Collaborative Rare Disease Flagship, Melbourne, Australia, 4Kidney Health Service and Conjoint Renal Research Laboratory, Royal Brisbane & Women’s Hospital and CKD.QLD and School of Medicine, University of Queensland, Brisbane, Brisbane, Australia, 5Sydney Genome Diagnostics, Westmead, Australia, 6Genetic Health Queensland, Royal Brisbane & Women’s Hospital, Brisbane, Australia, 7Department of Paediatrics, Centenary Hospital for Women and Children, Canberra, Australia , 8Department of Clinical Genetics, Royal Prince Alfred Hospital, Sydney, Australia, 9Royal Children’s Hospital , Melbourne, Australia
Aim: Review of test results from four years of renal gene panel testing.
Background: Genomic assessment is becoming a routine component of diagnostic work up for both paediatric and adult renal patients. Renal Genetic Clinics are established in almost all states and territories and access to sequencing is integral to their functionality. The ARGP service from Children’s Hospital at Westmead provides a regional NATA accredited diagnostic sequencing service for 22 renal gene panels.
Methods: A multidisciplinary team of nephrologists, clinical and molecular geneticists was established to curate the panels, review referrals/reports and provide advice if required to referring clinicians. Targeted exome panels utilise an Illumina TruSight One panel capture, sequencing using Illumina HiSeq 2500 or NextSeq 550 and variant classification is according to the ACMG guidelines. Gaps in genes of interest are backfilled as required using Sanger sequencing.
Results: 436 referrals for 414 families have been received from all New Zealand and all Australian states/territories (55% female and 51% paediatric at time of referral). In 39% of 315 reported results a disease causing variant (DCV) was found (13% variant of uncertain significance, 48% negative). Variants of interest were identified in 72 of the 225 genes represented, COL4A5 was reported 32 times. Detection rates did not differ significantly between adult and paediatric referrals except in Tubular/Metabolic renal panels (50% adults and 75% paediatric had a DCV); and AD tubulointerstitial disease (25% adults and 0% paediatric had a DCV).
Discussion: This regional service provides an expanded role in clinical advice/sequencing for health professionals investigating genetic aetiology of renal disease with increasing panels available. Future move to whole exome capture will further improve the diagnostic hit rate.
Dr Hugh McCarthy trained as a paediatric nephrologist in the UK where he completed his PhD in the genetics of steroid resistant nephrotic syndrome. This also involved establishing a national rare renal disease registry (RADAR); he is developing an Australasian equivalent registry (ARRK). Other than rare disease patient registries, his research interests include renal genomics and the pathogenesis of non genetic nephrotic syndrome.