The HIDDEN Protocol: An Australian Prospective Cohort Study to Determine the Utility of Whole Genome Sequencing in Kidney Failure of Unknown Aetiology

Frontiers in Medicine

Chirag Patel¹  Andrew John Mallett³  Jacqueline Soraru⁶  Zornitza Stark⁷  Catherine Quinlan⁷  Sadia Jahan⁸  Amali Mallawaarachchi⁹  Cas Simons^1,11  Alasdair Wood^1,11  Rosie O’Shea^1,11  Louise Wardrop^1,11 

[1] 0Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia;1Townsville University Hospital, Townsville, QLD, Australia;2College of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia;Australian Genomics, Murdoch Children’s Research Institute, Melbourne, VIC, Australia;Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia;Department of Nephrology and Hypertension, Perth Children’s Hospital, Perth, WA, Australia;Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia;Faculty of Medicine, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia;Garvan Institute of Medical Research, Sydney, NSW, Australia;Kidney Health Service, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia;Murdoch Children’s Research Institute, Melbourne, VIC, Australia;Royal Children’s Hospital, Melbourne, VIC, Australia;

关键词: kidney failure;    genomics;    genetic condition;    unknown aetiology;    genetic kidney disease;   

DOI  :  10.3389/fmed.2022.891223

来源: DOAJ

【 摘 要 】

Early identification of genetic kidney disease allows personalised management, clarification of risk for relatives, and guidance for family planning. Genetic disease is underdiagnosed, and recognition of genetic disease is particularly challenging in patients with kidney failure without distinguishing diagnostic features. To address this challenge, the primary aim of this study is to determine the proportion of genetic diagnoses amongst patients with kidney failure of unknown aetiology, using whole genome sequencing (WGS). A cohort of up to 100 Australian patients with kidney failure of unknown aetiology, with onset <50 years old and approved by a panel of study investigators will be recruited via 18 centres nationally. Clinically accredited WGS will be undertaken with analysis targeted to a priority list of ∼388 genes associated with genetic kidney disease. The primary outcome will be the proportion of patients who receive a molecular diagnosis (diagnostic rate) via WGS compared with usual -care (no further diagnostic investigation). Participant surveys will be undertaken at consent, after test result return and 1 year subsequently. Where there is no or an uncertain diagnosis, future research genomics will be considered to identify candidate genes and new pathogenic variants in known genes. All results will be relayed to participants via the recruiting clinician and/or kidney genetics clinic. The study is ethically approved (HREC/16/MH/251) with local site governance approvals in place. The future results of this study will be disseminated and inform practical understanding of the potential monogenic contribution to kidney failure of unknown aetiology. These findings are anticipated to impact clinical practice and healthcare policy.Study Registration[https://dora.health.qld.gov.au], identifier [HREC/16/MH/251].

【 授权许可】

Unknown