Novel SERAC1 Variant Presenting With Adult-Onset Extrapyramidal Dystonia-Parkinsonism Phenotype: A Case Report

Catherine Ashton; Mark Davis; Nigel Laing; Gianina Ravenscroft; Philipa Lamont

doi:10.1212/NXG.0000000000200067

Novel SERAC1 Variant Presenting With Adult-Onset Extrapyramidal Dystonia-Parkinsonism Phenotype: A Case Report

Neurol Genet. 2023 Mar 31;9(2):e200067. doi: 10.1212/NXG.0000000000200067. eCollection 2023 Apr.

Authors

Catherine Ashton¹, Mark Davis¹, Nigel Laing¹, Gianina Ravenscroft¹, Philipa Lamont¹

Affiliation

¹ Department of Neurogenetics (C.A., P.L.), Royal Perth Hospital, Perth, WA; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Nedlands; Centre for Medical Research (M.D., N.L., G.R.), University of Western Australia, Nedlands; and Harry Perkins Institute of Medical Research (N.L., G.R.), Nedlands, WA, Australia.

Abstract

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.