Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant

• Published in: Movement disorders clinical practice (Hoboken, N.J.) Vol. 11; no. 6; pp. 708 - 715
• Main Authors: Komulainen‐Ebrahim, Jonna, Kangas, Salla M., López‐Martín, Estrella, Feyma, Timothy, Scaglia, Fernando, Martínez‐Delgado, Beatriz, Kuismin, Outi, Suo‐Palosaari, Maria, Carr, Lucinda, Hinttala, Reetta, Kurian, Manju A., Uusimaa, Johanna
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2024
• Subjects: Child; cyclic; Female; Humans; Hyperkinesis - genetics; hyperkinetic; Male; Mitochondria - genetics; Mitochondria - pathology; movement disorder; Mutation, Missense; NACC1; Oxidative Phosphorylation; Repressor Proteins - genetics; movement disorder; hyperkinetic; cyclic; NACC1
• ISSN: 2330-1619; 2330-1619
• DOI: 10.1002/mdc3.14051

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.