Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing.

Autor: Macken WL; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK., Falabella M; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK., McKittrick C; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK., Pizzamiglio C; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK., Ellmers R; Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK., Eggleton K; Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK., Woodward CE; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK.; Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK., Patel Y; Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK., Labrum R; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK.; Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK., Phadke R; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Reilly MM; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK., DeVile C; Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Sarkozy A; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Footitt E; Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Davison J; Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.; National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, London, UK., Rahman S; Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.; Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK., Houlden H; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK., Bugiardini E; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK., Quinlivan R; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK.; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Hanna MG; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK., Vandrovcova J; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK. j.vandrovcova@ucl.ac.uk., Pitceathly RDS; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK. r.pitceathly@ucl.ac.uk.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK. r.pitceathly@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 07; Vol. 13 (1), pp. 6324. Date of Electronic Publication: 2022 Nov 07.
DOI: 10.1038/s41467-022-32908-7
Abstrakt: Diagnostic whole genome sequencing (WGS) is increasingly used in rare diseases. However, standard, semi-automated WGS analysis may overlook diagnoses in complex disorders. Here, we show that specialist multidisciplinary analysis of WGS, following an initial 'no primary findings' (NPF) report, improves diagnostic rates and alters management. We undertook WGS in 102 adults with diagnostically challenging primary mitochondrial disease phenotypes. NPF cases were reviewed by a genomic medicine team, thus enabling bespoke informatic approaches, co-ordinated phenotypic validation, and functional work. We enhanced the diagnostic rate from 16.7% to 31.4%, with management implications for all new diagnoses, and detected strong candidate disease-causing variants in a further 3.9% of patients. This approach presents a standardised model of care that supports mainstream clinicians and enhances diagnostic equity for complex disorders, thereby facilitating access to the potential benefits of genomic healthcare. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project: http://www.genomicsengland.co.uk .
(© 2022. The Author(s).)
Databáze: MEDLINE
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