ESPN 50th Annual Meeting

ESPN 2017


 
Australian Renal Gene Panels: Results from a national diagnostic service
Hugh McCarthy 1 Amali Mallawaarachchi 2 Chirag Patel 3 Gladys Ho 1 Katherine Holman 1 Andrew Mallett 3 Bruce Bennetts 1 Stephen Alexander 1

1- CHILDRENS HOSPITAL WESTMEAD
2- LIVERPOOL HOSPITAL, SYDNEY
3- ROYAL BRISBANE AND WOMENS HOSPITAL, BRISBANE
 
Introduction:

The reducing cost of massively parallel sequencing has enabled rapid incorporation into clinical practice. Judicious use will significantly aid in primary diagnostic investigations. 

Material and methods:

17 Renal Gene Panels have been developed at the department of Molecular Genetics at Children’s Hospital at Westmead by a multidisciplinary group of nephrologists, clinical and molecular geneticists according to reported association with renal phenotypes. Referrals were accepted from Aug 2014. 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:

43% 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 80% and 88% respectively; Tubular 75% both). However, where a condition displays heterogeneous genetic aetiology, detection rate was generally higher in the paediatric compared to the adult cohort (Complement mediated disease 64% vs. 17% and Ciliopathies 47% vs. 29%). Identification in the nephrotic cohort was even (33% vs. 32%) which reflects a differing threshold for referral by adult and paediatric clinicians.

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.