Diagnostic Renal Gene Panel Results Reflect A Higher Prevalence Of Genetic Aetiology In Childhood Onset Renal Disease

Abstract

Aim: To compare the rate of positive identification of disease causing variants inpaediatricand adultpatients referred for diagnostic renal gene panels. Background:Thereducingcostofmassivelyparallelsequencing has enabled rapid incorporation into clinical practice. Judicious use will significantly aid in primary diagnostic investigations.However,notallgenetictestshaveasimilarrate of detection. Methods: 9 Renal Gene Panels were developed at the departmentofMolecularGeneticsatChildren’sHospitalatWestmead by a multidisciplinary group of nephrologists, clinical and molecular geneticists according to reported association with renal phenotypes. Sequencing was performed using an Illumina TruSight One panel capture on an Illumina HiSeq platform with analysis using NextGene bioinformatics pipeline. Genes of interest were backfilled as required. Pathogenic variants were confirmed with Sanger sequencing. Results: 57 paediatric and 56 adult renal patients were referred from 6 states/territories. 42% of patients had an identifiable disease-causing variant. Where clinical phenotype is clearly defined, the diagnostic rate was high in both adult and paediatric cohorts (Alport’s 81% and 88% respectively; Tubular 75% both). However, where a condition displays heterogeneous aetiology and genetic association, detection rate was higher in the paediatric compared to the adult cohort (Complement mediated disease 57% vs. 19%; Nephrotic Syndrome 38% vs. 25%; and Ciliopathies 38% vs. 14%). Conclusions: The use of genetic analysis is now available to Australasian clinicians and renal patients. However, the rate of detection differs according to age at presentation and renal phenotype.Using this information,clinicians can better counsel at the time of consenting patients for diagnostic genetic testing and provide higher fidelity phenotypic information to genetic diagnostic laboratories. Show more