Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease.
Adolescent
Adult
Charcot-Marie-Tooth Disease
/ genetics
Child
Child, Preschool
Comparative Genomic Hybridization
Cytoskeletal Proteins
/ genetics
DNA Copy Number Variations
/ genetics
Exome
/ genetics
Female
Genetic Predisposition to Disease
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Microfilament Proteins
/ genetics
Middle Aged
Mutation
/ genetics
Nerve Tissue Proteins
/ genetics
Phenotype
Ubiquitin-Protein Ligases
/ genetics
Exome Sequencing
Young Adult
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
20
09
2019
accepted:
08
12
2019
revised:
03
12
2019
pubmed:
20
12
2019
medline:
10
10
2020
entrez:
20
12
2019
Statut:
ppublish
Résumé
Charcot-Marie-Tooth disease (CMT) is a hereditary sensory-motor neuropathy characterized by a strong clinical and genetic heterogeneity. Over the past few years, with the occurrence of whole-exome sequencing (WES) or whole-genome sequencing (WGS), the molecular diagnosis rate has been improved by allowing the screening of more than 80 genes at one time. In CMT, except the recurrent PMP22 duplication accounting for about 60% of pathogenic variations, pathogenic copy number variations (CNVs) are rarely reported and only a few studies screening specifically CNVs have been performed. The aim of the present study was to screen for CNVs in the most prevalent genes associated with CMT in a cohort of 200 patients negative for the PMP22 duplication. CNVs were screened using the Exome Depth software on next generation sequencing (NGS) data obtained by targeted capture and sequencing of a panel of 81 CMT associated genes. Deleterious CNVs were identified in four patients (2%), in four genes: GDAP1, LRSAM1, GAN, and FGD4. All CNVs were confirmed by high-resolution oligonucleotide array Comparative Genomic Hybridization (aCGH) and/or quantitative PCR. By identifying four new CNVs in four different genes, we demonstrate that, although they are rare mutational events in CMT, CNVs might contribute significantly to mutational spectrum of Charcot-Marie-Tooth disease and should be searched in routine NGS diagnosis. This strategy increases the molecular diagnosis rate of patients with neuropathy.
Identifiants
pubmed: 31852984
doi: 10.1038/s10038-019-0710-5
pii: 10.1038/s10038-019-0710-5
doi:
Substances chimiques
Cytoskeletal Proteins
0
FGD4 protein, human
0
GAN protein, human
0
GDAP protein
0
Microfilament Proteins
0
Nerve Tissue Proteins
0
LRSAM1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
313-323Références
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