Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Affiliations

PMID: 32939031
DOI: 10.1038/s41436-020-00963-4

Free article

Abstract

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.

Keywords: chronic kidney disease; exome sequencing; genetic kidney disease.

Similar articles

Diagnostic Impact and Cost-effectiveness of Whole-Exome Sequencing for Ambulant Children With Suspected Monogenic Conditions.
Tan TY, Dillon OJ, Stark Z, Schofield D, Alam K, Shrestha R, Chong B, Phelan D, Brett GR, Creed E, Jarmolowicz A, Yap P, Walsh M, Downie L, Amor DJ, Savarirayan R, McGillivray G, Yeung A, Peters H, Robertson SJ, Robinson AJ, Macciocca I, Sadedin S, Bell K, Oshlack A, Georgeson P, Thorne N, Gaff C, White SM.JAMA Pediatr. 2017 Sep 1;171(9):855-862. doi: 10.1001/jamapediatrics.2017.1755.PMID: 28759686 Free PMC article.
Comprehensive evaluation of a prospective Australian patient cohort with suspected genetic kidney disease undergoing clinical genomic testing: a study protocol.
Jayasinghe K, Stark Z, Patel C, Mallawaarachchi A, McCarthy H, Faull R, Chakera A, Sundaram M, Jose M, Kerr P, Wu Y, Wardrop L, Goranitis I, Best S, Martyn M, Quinlan C, Mallett AJ.BMJ Open. 2019 Aug 5;9(8):e029541. doi: 10.1136/bmjopen-2019-029541.PMID: 31383705 Free PMC article.
A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.
Stark Z, Tan TY, Chong B, Brett GR, Yap P, Walsh M, Yeung A, Peters H, Mordaunt D, Cowie S, Amor DJ, Savarirayan R, McGillivray G, Downie L, Ekert PG, Theda C, James PA, Yaplito-Lee J, Ryan MM, Leventer RJ, Creed E, Macciocca I, Bell KM, Oshlack A, Sadedin S, Georgeson P, Anderson C, Thorne N, Melbourne Genomics Health Alliance, Gaff C, White SM.Genet Med. 2016 Nov;18(11):1090-1096. doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.PMID: 26938784
The cost and diagnostic yield of exome sequencing for children with suspected genetic disorders: a benchmarking study.
Dragojlovic N, Elliott AM, Adam S, van Karnebeek C, Lehman A, Mwenifumbo JC, Nelson TN, du Souich C, Friedman JM, Lynd LD.Genet Med. 2018 Sep;20(9):1013-1021. doi: 10.1038/gim.2017.226. Epub 2018 Jan 4.PMID: 29300375 Review.
Personalized medicine in chronic kidney disease by detection of monogenic mutations.
Connaughton DM, Hildebrandt F.Nephrol Dial Transplant. 2020 Mar 1;35(3):390-397. doi: 10.1093/ndt/gfz028.PMID: 30809662 Free PMC article. Review.