Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

Ann Neurol. 2023 Feb;93(2):330-335. doi: 10.1002/ana.26544. Epub 2022 Nov 18.

Abstract

Infantile striatonigral degeneration is caused by a homozygous variant of the nuclear-pore complex (NPC) gene NUP62, involved in nucleo-cytoplasmic trafficking. By querying sequencing-datasets of patients with dystonia and/or Leigh(-like) syndromes, we identified 3 unrelated individuals with biallelic variants in NUP54. All variants clustered in the C-terminal protein region that interacts with NUP62. Associated phenotypes were similar to those of NUP62-related disease, including early-onset dystonia with dysphagia, choreoathetosis, and T2-hyperintense lesions in striatum. In silico and protein-biochemical studies gave further evidence for the argument that the variants were pathogenic. We expand the spectrum of NPC component-associated dystonic conditions with localized basal-ganglia abnormalities. ANN NEUROL 2023;93:330-335.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Corpus Striatum
  • Dystonia* / genetics
  • Dystonic Disorders* / genetics
  • Humans
  • Neostriatum
  • Nuclear Pore Complex Proteins* / genetics

Substances

  • Nuclear Pore Complex Proteins
  • NUP54 protein, human