Phenotypical and Myopathological Consequences of Compound Heterozygous Missense and Nonsense Variants in
Acetylcholine
/ biosynthesis
Animals
Child, Preschool
Codon, Nonsense
/ genetics
Disease Models, Animal
Humans
Male
Mice
Muscle Fibers, Skeletal
/ metabolism
Mutation, Missense
/ genetics
Myasthenic Syndromes, Congenital
/ genetics
Neuromuscular Junction
/ genetics
Vesicular Acetylcholine Transport Proteins
/ genetics
Exome Sequencing
CARS microscopy
SLC18A1
congenital myasthenic syndrome
lipid accumulation
muscle biopsy
vesicular acetylcholine transporter (VAChT)
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
09 12 2021
09 12 2021
Historique:
received:
17
10
2021
revised:
11
11
2021
accepted:
12
11
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
18
1
2022
Statut:
epublish
Résumé
Presynaptic forms of congenital myasthenic syndromes (CMS) due to pathogenic variants in Exome sequencing (ES) was carried out to identify the molecular genetic cause of the disease in a 5-year-old male patient and histological, immunofluorescence as well as electron- and CARS-microscopic studies were performed to delineate the muscle pathology, which has so far only been studied in VAChT-deficient animal models. ES unraveled compound heterozygous missense and nonsense variants (c.315G>A, p.Trp105* and c.1192G>C, p.Asp398His) in We suggest that nonsense variants have a more detrimental impact on the clinical manifestation of
Sections du résumé
BACKGROUND
Presynaptic forms of congenital myasthenic syndromes (CMS) due to pathogenic variants in
METHODS
Exome sequencing (ES) was carried out to identify the molecular genetic cause of the disease in a 5-year-old male patient and histological, immunofluorescence as well as electron- and CARS-microscopic studies were performed to delineate the muscle pathology, which has so far only been studied in VAChT-deficient animal models.
RESULTS
ES unraveled compound heterozygous missense and nonsense variants (c.315G>A, p.Trp105* and c.1192G>C, p.Asp398His) in
CONCLUSIONS
We suggest that nonsense variants have a more detrimental impact on the clinical manifestation of
Identifiants
pubmed: 34943989
pii: cells10123481
doi: 10.3390/cells10123481
pmc: PMC8700530
pii:
doi:
Substances chimiques
Codon, Nonsense
0
SLC18A3 protein, human
0
Slc18a3 protein, mouse
0
Vesicular Acetylcholine Transport Proteins
0
Acetylcholine
N9YNS0M02X
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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