Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

Philip Harrer , Audrey Schalk , Masaru Shimura , Sarah Baer (1, 2) , Nadege Calmels (3) , Marie Aude Spitz , Marie-Thérèse Abi Warde , Elise Schaefer (3) , Volker M. Sc Kittke , Yasemin Dincer , Matias Wagner , Ivana Dzinovic , Riccardo Berutti , Tatsuharu Sato , Toshihiko Shirakawa , Yasushi Okazaki , Kei Murayama , Konrad Oexle , Holger Prokisch , Volker Mall , Ivo Melčák , Juliane Winkelmann , Michael Zech

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
3 LGM - Laboratoire de Génétique Médicale

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.

Domaines: Neurosciences [q-bio.NC]

Philip Harrer, Audrey Schalk, Masaru Shimura, Sarah Baer, Nadege Calmels, et al.. Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions. Annals of Neurology, 2023, 93 (2), pp.330-335. ⟨10.1002/ana.26544⟩. ⟨hal-04225567⟩