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

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

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.

MOVEMENT disorders; MISSENSE mutation; ATTENTION-deficit hyperactivity disorder; MITOCHONDRIAL proteins; OXIDATIVE phosphorylation; CELL physiology

Movement Disorders Clinical Practice, 2024, Vol 11, Issue 6, p708

2330-1619

Academic Journal

10.1002/mdc3.14051