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

Humans Rare Diseases / diagnosis Whole Genome Sequencing Phenotype Genome

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 11 2022
Historique:
received: 14 03 2022
accepted: 24 08 2022
entrez: 7 11 2022
pubmed: 8 11 2022
medline: 10 11 2022
Statut: epublish

Résumé

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 .

Identifiants

DOI: 10.1038/s41467-022-32908-7 PMID: 36344503 PMC: PMC9640711
pubmed: 36344503
doi: 10.1038/s41467-022-32908-7
pii: 10.1038/s41467-022-32908-7
pmc: PMC9640711
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6324

Subventions

Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S002065/1
Pays : United Kingdom

Investigateurs

J C Ambrose (JC)
P Arumugam (P)
R Bevers (R)
M Bleda (M)
F Boardman-Pretty (F)
C R Boustred (CR)
H Brittain (H)
M A Brown (MA)
M J Caulfield (MJ)
G C Chan (GC)
A Giess (A)
J N Griffin (JN)
A Hamblin (A)
S Henderson (S)
T J P Hubbard (TJP)
R Jackson (R)
L J Jones (LJ)
D Kasperaviciute (D)
M Kayikci (M)
A Kousathanas (A)
L Lahnstein (L)
A Lakey (A)
S E A Leigh (SEA)
I U S Leong (IUS)
F J Lopez (FJ)
F Maleady-Crowe (F)
M McEntagart (M)
F Minneci (F)
J Mitchell (J)
L Moutsianas (L)
M Mueller (M)
N Murugaesu (N)
A C Need (AC)
P O'Donovan (P)
C A Odhams (CA)
C Patch (C)
D Perez-Gil (D)
M B Pereira (MB)
J Pullinger (J)
T Rahim (T)
A Rendon (A)
T Rogers (T)
K Savage (K)
K Sawant (K)
R H Scott (RH)
A Siddiq (A)
A Sieghart (A)
S C Smith (SC)
A Sosinsky (A)
A Stuckey (A)
M Tanguy (M)
A L Taylor Tavares (AL)
E R A Thomas (ERA)
S R Thompson (SR)
A Tucci (A)
M J Welland (MJ)
E Williams (E)
K Witkowska (K)
S M Wood (SM)
M Zarowiecki (M)

Informations de copyright

© 2022. The Author(s).

Références

N Engl J Med. 2021 Nov 11;385(20):1868-1880
pubmed: 34758253
Mol Genet Metab. 2016 Aug;118(4):230-1
pubmed: 27211610
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Genet Med. 2017 Sep;19(9):1040-1048
pubmed: 28252636
Neurology. 2018 Nov 27;91(22):e2078-e2088
pubmed: 30413629
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
BMJ. 2018 Apr 24;361:k1687
pubmed: 29691228
Genet Med. 2021 Oct;23(10):1933-1943
pubmed: 34172899
NPJ Genom Med. 2018 Aug 6;3:19
pubmed: 30109123
BMJ. 2021 Nov 3;375:e066288
pubmed: 34732400
Nat Commun. 2017 Jun 12;8:15824
pubmed: 28604674
J Med Genet. 2022 Aug;59(8):737-747
pubmed: 34716235
Genet Med. 2020 Jul;22(7):1254-1261
pubmed: 32313153
Cell. 2019 Jan 24;176(3):535-548.e24
pubmed: 30661751
Nat Genet. 2019 Nov;51(11):1560-1565
pubmed: 31676867
Bioinformatics. 2016 Apr 15;32(8):1220-2
pubmed: 26647377
Neurology. 2006 Nov 28;67(10):1823-6
pubmed: 17130416
Nat Rev Neurol. 2021 Apr;17(4):215-230
pubmed: 33623159
Genet Med. 2020 Jun;22(6):1005-1014
pubmed: 32123317
Genet Med. 2021 Dec;23(12):2360-2368
pubmed: 34429528
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Genome Med. 2019 Dec 31;12(1):5
pubmed: 31892366
Clin Genet. 2017 Oct;92(4):447-448
pubmed: 28542708
Nat Protoc. 2015 Dec;10(12):2004-15
pubmed: 26562621

Auteurs

William L 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.
ORCID: 0000-0003-0612-5819

Micol Falabella (M)

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
ORCID: 0000-0002-1020-1848

Caroline McKittrick (C)

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.

Chiara 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.
ORCID: 0000-0001-5519-0313

Rebecca Ellmers (R)

Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK.

Kelly Eggleton (K)

Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK.

Cathy E 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.

Yogen Patel (Y)

Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK.

Robyn 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.

Rahul Phadke (R)

Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Mary M Reilly (MM)

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.

Catherine DeVile (C)

Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Anna Sarkozy (A)

Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Emma Footitt (E)

Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

James 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.

Shamima 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.
ORCID: 0000-0003-2088-730X

Henry Houlden (H)

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
ORCID: 0000-0002-2866-7777

Enrico 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.

Rosaline 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.

Michael G 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.

Jana Vandrovcova (J)

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK. j.vandrovcova@ucl.ac.uk.

Robert D S 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.
ORCID: 0000-0002-6123-4551

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Specialist multidisciplinary input maximises...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladies rares › Specialist multidisciplinary input maximises...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Specialist multidisciplinary input maximises...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Specialist multidisciplinary input maximises...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Specialist multidisciplinary input maximises...