Abstract
BackgroundA multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit. Here we describe the results of establishing a genomic medicine multi-disciplinary team (GM-MDT) for case selection, processing, interpretation and return of results.MethodsWe report a consecutive case series of 132 patients (involving 10 medical specialties with 43.2% cases having a neurological disorder) undergoing exome sequencing over a 10-month period following the establishment of the GM-MDT in a UK NHS tertiary referral hospital. The costs of running the MDT are also reported.ResultsIn total 76 cases underwent exome sequencing following triage by the GM-MDT with a clinically reportable molecular diagnosis in 24 (31.6%). GM-MDT composition, operation and rationale for whether to proceed to sequencing are described, together with the health economics (cost per case for the GM-MDT was £399.61), the utility and informativeness of exome sequencing for molecular diagnosis in a range of traits, the impact of choice of sequencing strategy on molecular diagnostic rates and challenge of defining pathogenic variants. In 5 cases (6.6%), an alternative clinical diagnosis was indicated by sequencing results. Examples were also found where findings from initial genetic testing were reconsidered in the light of exome sequencing including TP63 and PRKAG2 (detection of a partial exon deletion and a mosaic missense pathogenic variant respectively); together with tissue-specific mosaicism involving a cytogenetic abnormality following a normal prenatal array comparative genomic hybridization.ConclusionsThis consecutive case series describes the results and experience of a multidisciplinary team format that was found to promote engagement across specialties and facilitate return of results to the responsible clinicians.
Highlights
A multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit
genomic medicine multi-disciplinary team (GM-MDT) process and prospective exome sequencing (ES) cohort The GM-MDT was established as an initiative supported by the Oxford National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) through a process of outreach and education across clinical specialty areas with clinicians participating from 11 specialties together with genetic counsellors, ethicists, bioinformaticians, non-clinical researchers and clinical scientists from the Oxford Molecular Genetics Laboratory (Additional file 1: Table S1)
This most commonly involved array comparative genomic hybridization testing and single gene(s) sequencing while gene panel testing, mitochondrial gene sequencing, karyotyping, metabolic workup and immunological testing were performed in a minority of cases (Fig. 2b)
Summary
A multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit. There is recognition that while rapid technological advances and reducing cost have made adoption of genome-scale NGS a realistic goal, effective implementation into the clinic for direct patient benefit remains challenging, with many current barriers to widespread adoption These range from a demonstration of improvement in patient outcomes and cost-effectiveness, to practical difficulties involving physician support and education, establishing pathogenicity for identified variants, handling large complex datasets, dealing with secondary findings whether incidental or sought, and managing the expectations of the patient, clinician and general population [7]. We focus on the operation and impact of the GM-MDT, including a prospective case series involving exome sequencing (ES) and health system costs for running the GM-MDT
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