Ashton_2023_Neurol.Genet_9_e200067

OBJECTIVES: To report a novel likely pathogenic variant in the SERAC1 gene associated with early adult-onset parkinsonism and progressive dystonia. METHODS: Clinical, biochemical, and imaging assessments were performed on 2 affected adult brothers with a genetically unsolved progressive neurologic disorder followed by whole-genome sequencing. RESULTS: A homozygous likely pathogenic variant in the SERAC1 gene (c.[129-2A > C], p.[(?)];[(?)]) was discovered. DISCUSSION: We describe a novel homozygous variant in the serine active site-containing protein 1 gene (SERAC1) in 2 brothers with a progressive extrapyramidal movement disorder of early onset parkinsonism and dystonia. Previous variants have been associated with a severe 3-methylglutaconic aciduria with dystonia, deafness, hepatopathy, encephalopathy and Leigh-like syndrome, or juvenile onset complicated spastic paraparesis. Our cases expand the phenotype of SERAC1 variants, with an adult-onset presentation of dystonia-parkinsonism.