Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges.
Journal
Nature reviews. Neurology
ISSN: 1759-4766
Titre abrégé: Nat Rev Neurol
Pays: England
ID NLM: 101500072
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
accepted:
12
08
2019
pubmed:
5
10
2019
medline:
30
1
2020
entrez:
5
10
2019
Statut:
ppublish
Résumé
Charcot-Marie-Tooth disease and the related disorders hereditary motor neuropathy and hereditary sensory neuropathy, collectively termed CMT, are the commonest group of inherited neuromuscular diseases, and they exhibit wide phenotypic and genetic heterogeneity. CMT is usually characterized by distal muscle atrophy, often with foot deformity, weakness and sensory loss. In the past decade, next-generation sequencing (NGS) technologies have revolutionized genomic medicine and, as these technologies are being applied to clinical practice, they are changing our diagnostic approach to CMT. In this Review, we discuss the application of NGS technologies, including disease-specific gene panels, whole-exome sequencing, whole-genome sequencing (WGS), mitochondrial sequencing and high-throughput transcriptome sequencing, to the diagnosis of CMT. We discuss the growing challenge of variant interpretation and consider how the clinical phenotype can be combined with genetic, bioinformatic and functional evidence to assess the pathogenicity of genetic variants in patients with CMT. WGS has several advantages over the other techniques that we discuss, which include unparalleled coverage of coding, non-coding and intergenic areas of both nuclear and mitochondrial genomes, the ability to identify structural variants and the opportunity to perform genome-wide dense homozygosity mapping. We propose an algorithm for incorporating WGS into the CMT diagnostic pathway.
Identifiants
pubmed: 31582811
doi: 10.1038/s41582-019-0254-5
pii: 10.1038/s41582-019-0254-5
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
644-656Subventions
Organisme : NINDS NIH HHS
ID : U54 NS065712
Pays : United States
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doi: 10.1002/acn3.409