GGC repeat expansions in NOTCH2NLC causing a phenotype of lower motor neuron syndrome.
Lower motor neuron syndrome
Motor neuron disease
NOTCH2NLC gene
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
02
01
2022
accepted:
18
03
2022
revised:
14
03
2022
pubmed:
4
4
2022
medline:
22
7
2022
entrez:
3
4
2022
Statut:
ppublish
Résumé
A genetic diagnosis cannot be made in a considerable proportion of patients with hereditary lower motor neuron (LMN) syndromes. The GGC repeat expansion in the 5'untranslated region (5'UTR) of NOTCH2NLC gene has been reported to be associated with a group of NOTCH2NLC-related repeat expansion disorders (NRED), including amyotrophic lateral sclerosis (ALS). The relationship between the mutation and LMN syndromes has not been reported previously. Here, we identified the GGC repeat expansions of NOTCH2NLC in a Chinese familial patient with LMN syndrome, presenting with slowly progressive weakness of four limbs. Needle electromyography revealed evidence of acute denervation and chronic neurogenic changes. Cognition and brain MRI were normal. Initial whole-exome sequencing by next generation sequencing revealed negative results. However, repeat-primed polymerase chain reaction performed on the proband showed a pathogenic GGC expansion in the 5'UTR of NOTCH2NLC and long-read sequencing subsequently revealed 248 GGC repeats. The mutation was co-segregated with the clinical phenotype in the family. Immunofluorescent studies identified p62-positive protein deposits in the intranuclear inclusions in myofibers. The GGC repeat expansion in NOTCH2NLC is associated with a new phenotype of hereditary LMN syndrome. As a result, NOTCH2NLC genotyping should be performed in patients with hereditary LMN syndromes.
Identifiants
pubmed: 35366689
doi: 10.1007/s00415-022-11092-0
pii: 10.1007/s00415-022-11092-0
doi:
Substances chimiques
5' Untranslated Regions
0
Intercellular Signaling Peptides and Proteins
0
NOTCH2NLC protein, human
0
Nerve Tissue Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4469-4477Subventions
Organisme : Health Commission of Shanxi Province
ID : 2019034
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
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