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BMC Nephrol. 2015 Sep 15;16:152. doi: 10.1186/s12882-015-0148-8.

A protocol for the identification and validation of novel genetic causes of kidney disease.

Author information

1
Kidney Health Service and Conjoint Kidney Research Laboratory, Royal Brisbane and Women's Hospital, Brisbane, Australia. Andrew.mallett@health.qld.gov.au.
2
Centre for Kidney Disease Research, Centre for Chronic Disease and CKD.QLD, School of Medicine, The University of Queensland, St Lucia, Australia. Andrew.mallett@health.qld.gov.au.
3
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia. Andrew.mallett@health.qld.gov.au.
4
Kidney Health Service, Level 9, Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Brisbane, Qld, 4029, Australia. Andrew.mallett@health.qld.gov.au.
5
Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia.
6
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.
7
Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
8
School of Medicine, Griffith University, Brisbane, Australia.
9
Centre for Kidney Disease Research, Centre for Chronic Disease and CKD.QLD, School of Medicine, The University of Queensland, St Lucia, Australia.
10
Queensland Child and Adolescent Renal Service, Lady Cilento Children's Hospital, Brisbane, Australia.
11
Department of Nephrology, Children's Hospital at Westmead, Sydney and Sydney Medical School, The University of Sydney, Sydney, Australia.
12
Department of Nephrology, Westmead Hospital, Sydney and Sydney Medical School, The University of Sydney, Sydney, Australia.
13
Department of Genetic Medicine, Westmead Hospital, Sydney and Sydney Medical School, The University of Sydney, Sydney, Australia.
14
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia.
15
Kidney Health Service and Conjoint Kidney Research Laboratory, Royal Brisbane and Women's Hospital, Brisbane, Australia.
16
Department of Nephrology, Royal Children's Hospital, Melbourne, Australia.
17
Molecular Genetics Laboratory, Pathology Queensland and Royal Brisbane and Women's Hospital, Brisbane, Australia.
18
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Australia.
19
Department of Paediatrics, University of Melbourne, Melbourne, Australia.

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.

PMID:
26374634
PMCID:
PMC4570515
DOI:
10.1186/s12882-015-0148-8
[Indexed for MEDLINE]
Free PMC Article

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