Australia and New Zealand renal gene panel testing in routine clinical practice of 542 families

Hope A Tanudisastro,Stephen I Alexander,Katherine Holman,Andrew J Mallett,Hugh J Mccarthy,Gladys Ho,Chirag Patel,Tiffany Lai,Thet Gayagay,Katrina Fisk,Bruce Bennetts,Rahul Krishnaraj,Elizabeth Farnsworth,Emma Hackett,Gemma Jenkins,Karen Wong,Amali Mallawaarachchi

doi:10.1038/s41525-021-00184-x

Abstract

Genetic testing in nephrology clinical practice has moved rapidly from a rare specialized test to routine practice both in pediatric and adult nephrology. However, clear information pertaining to the likely outcome of testing is still missing. Here we describe the experience of the accredited Australia and New Zealand Renal Gene Panels clinical service, reporting on sequencing for 552 individuals from 542 families with suspected kidney disease in Australia and New Zealand. An increasing number of referrals have been processed since service inception with an overall diagnostic rate of 35%. The likelihood of identifying a causative variant varies according to both age at referral and gene panel. Although results from high throughput genetic testing have been primarily for diagnostic purposes, they will increasingly play an important role in directing treatment, genetic counseling, and family planning.

Highlights

Kidney disease can present in a number of ways in children and adults, either as isolated cases or with a family history[1]
We evaluate the use of massively parallel sequencing in kidney disease by health professionals across Australia and New Zealand and quantify the frequency of disease-causing variant identification
We extend the analysis of the diagnostic utility of kidney gene panels from our initial report of 135 families in 20175 to include over 500 patients, the largest cohort of Australian and New Zealand kidney patients reported to date

Summary

INTRODUCTION

Kidney disease can present in a number of ways in children and adults, either as isolated cases or with a family history[1]. Several recent international reports of testing in large cohorts of non-specific chronic kidney disease (CKD) and more directed testing of children with kidney disease have shown diagnostic rates of between 9 and 42%2–4, approximately in line with our previous report on gene panel testing in 135 Australian and New Zealand families with a diagnostic rate of 43%5. As genetic sequencing becomes more accessible as a routine tool in the diagnostic work up of a patient or family with kidney disease, quantifying the use by clinicians provides an understanding of the need for future training and education in genomic literacy among nephrologists, both adult and pediatric based. We evaluate the use of massively parallel sequencing in kidney disease by health professionals across Australia and New Zealand and quantify the frequency of disease-causing variant identification. We extend the analysis of the diagnostic utility of kidney gene panels from our initial report of 135 families in 20175 to include over 500 patients, the largest cohort of Australian and New Zealand kidney patients reported to date

RESULTS

DISCUSSION

Ethical approval