Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant.
NACC1
cyclic
hyperkinetic
movement disorder
Journal
Movement disorders clinical practice
ISSN: 2330-1619
Titre abrégé: Mov Disord Clin Pract
Pays: United States
ID NLM: 101630279
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
revised:
10
02
2024
received:
17
10
2023
accepted:
25
03
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
3
5
2024
Statut:
aheadofprint
Résumé
Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency. The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level. The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts. All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient. The movement disorder is a prominent feature of NACC1-related disease.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency.
OBJECTIVES
OBJECTIVE
The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level.
METHODS
METHODS
The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts.
RESULTS
RESULTS
All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient.
CONCLUSIONS
CONCLUSIONS
The movement disorder is a prominent feature of NACC1-related disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/S020136/1
Pays : United Kingdom
Organisme : CLC NIH HHS
ID : 5U54-NS078059
Pays : United States
Organisme : CLC NIH HHS
ID : 5U54-NS115198 03
Pays : United States
Organisme : FDA HHS
ID : 5R01-FD005407
Pays : United States
Informations de copyright
© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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