Komulainen-Ebrahim, JonnaKangas, Salla MLopez-Martin, EstrellaFeyma, TimothyScaglia, FernandoMartinez-Delgado, BeatrizKuismin, OutiSuo-Palosaari, MariaCarr, LucindaHinttala, ReettaKurian, Manju AUusimaa, Johanna2024-10-092024-10-092024-06Mov Disord Clin Pract. 2024 Jun;11(6):708-715.2330-1619https://hdl.handle.net/20.500.12105/25074Background: 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.engVoRhttp://creativecommons.org/licenses/by/4.0/NACC1CyclicHyperkineticMovement disorderChildFemaleHumansHyperkinesisMaleMitochondriaMutation, MissenseOxidative PhosphorylationRepressor ProteinsAttribution 4.0 International38698576116708-71510.1002/mdc3.14051Movement disorders clinical practiceopen access