The rare and undiagnosed diseases diagnostic service – application of massively parallel sequencing in a state-wide clinical service

Gareth Baynam, Nicholas Pachter, Fiona McKenzie, Sharon Townshend, Jennie Slee, Cathy Kiraly-Borri, Anand Vasudevan, Anne Hawkins, Stephanie Broley, Lyn Schofield, Hedwig Verhoef, Caroline E. Walker, Caron Molster, Jenefer M. Blackwell, Sarra Jamieson, Dave Tang, Timo Lassmann, Kym Mina, John Beilby, Mark Davis, Nigel Laing, Lesley Murphy, Tarun Weeramanthri, Hugh Dawkins, Jack Goldblatt

The Rare and Undiagnosed Diseases Diagnostic Service (RUDDS) refers to a genomic diagnostic platform operating within the Western Australian Government clinical services delivered through Genetic Services of Western Australia (GSWA). GSWA has provided a state-wide service for clinical genetic care for 28 years and it serves a population of 2.5 million people across a geographical area of 2.5milion Km(2). Within this context, GSWA has established a clinically integrated genomic diagnostic platform in partnership with other public health system managers and service providers, including but not limited to the Office of Population Health Genomics, Diagnostic Genomics (PathWest Laboratories) and with executive level support from the Department of Health. Herein we describe report presents the components of this service that are most relevant to the heterogeneity of paediatric clinical genetic care. Briefly the platform : i) offers multiple options including non-genetic testing; monogenic and genomic (targeted in silico filtered and whole exome) analysis; and matchmaking; ii) is delivered in a patient-centric manner that is resonant with the patient journey, it has multiple points for entry, exit and re-entry to allow people access to information they can use, when they want to receive it; iii) is synchronous with precision phenotyping methods; iv) captures new knowledge, including multiple expert review; v) is integrated with current translational genomic research activities and best practice; and vi) is designed for flexibility for interactive generation of, and integration with, clinical research for diagnostics, community engagement, policy and models of care. The RUDDS has been established as part of routine clinical genetic services and is thus sustainable, equitably managed and seeks to translate new knowledge into efficient diagnostics and improved health for the whole community.