Mallett, Andrew, Patel, Chirag, Maier, Barbara, McGaughran, Julie, Gabbett, Michael, Takasato, Minoru, Cameron, Anne, Trnka, Peter, Alexander, Stephen I., Rangan, Gopala, Tchan, Michel C., Caruana, Georgina, John, George, Quinlan, Cathy, Mccarthy, Hugh J., Hyland, Valentine, Hoy, Wendy E., Wolvetang, Ernst, Taft, Ryan, Simons, Cas, Healy, Helen, and Little, Melissa (2015) A protocol for the identification and validation of novel genetic causes of kidney disease. BMC Nephrology, 16. 152.

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Abstract

Background: Genetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10 % of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD.

Methods/Design: This study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra-renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed.

Discussion: This investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology.

Item ID:	67892
Item Type:	Article (Scholarly Work)
ISSN:	1471-2369
Copyright Information:	© 2015 Mallett et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0. International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Date Deposited:	18 Dec 2024 01:15
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320214 Nephrology and urology @ 70% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320213 Medical genetics (excl. cancer genetics) @ 30%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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