Publication Date
6-1-2024
Journal
Movement Disorders Clinical Practice
DOI
10.1002/mdc3.14051
PMID
38698576
PMCID
PMC11145100
PubMedCentral® Posted Date
5-2-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Child, Female, Humans, Male, Hyperkinesis, Mitochondria, Mutation, Missense, Oxidative Phosphorylation, Repressor Proteins, cyclic, hyperkinetic, movement disorder, NACC1
Abstract
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: 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: 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: 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: The movement disorder is a prominent feature of NACC1-related disease.
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