TY - JOUR
T1 - Clinical impact of genomic testing in patients with suspected monogenic kidney disease
AU - Jayasinghe, Kushani
AU - Stark, Zornitza
AU - Kerr, Peter G.
AU - Gaff, Clara
AU - Martyn, Melissa
AU - Whitlam, John
AU - Creighton, Belinda
AU - Donaldson, Elizabeth
AU - Hunter, Matthew
AU - Jarmolowicz, Anna
AU - Johnstone, Lilian
AU - Krzesinski, Emma
AU - Lunke, Sebastian
AU - Lynch, Elly
AU - Nicholls, Kathleen
AU - Patel, Chirag
AU - Prawer, Yael
AU - Ryan, Jessica
AU - See, Emily J.
AU - Talbot, Andrew
AU - Trainer, Alison
AU - Tytherleigh, Rigan
AU - Valente, Giulia
AU - Wallis, Mathew
AU - Wardrop, Louise
AU - West, Kirsty H.
AU - White, Susan M.
AU - Wilkins, Ella
AU - Mallett, Andrew J.
AU - Quinlan, Catherine
PY - 2021/1
Y1 - 2021/1
N2 - Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.
AB - Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.
KW - chronic kidney disease
KW - exome sequencing
KW - genetic kidney disease
UR - http://www.scopus.com/inward/record.url?scp=85091040424&partnerID=8YFLogxK
U2 - 10.1038/s41436-020-00963-4
DO - 10.1038/s41436-020-00963-4
M3 - Article
C2 - 32939031
AN - SCOPUS:85091040424
SN - 1098-3600
VL - 23
SP - 183
EP - 191
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 1
ER -