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

Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

Philip Harrer  1   2 , Audrey Schalk  3 , Masaru Shimura  1   4 , Sarah Baer  5   6 , Nadège Calmels  3   7 , Marie Aude Spitz  5 , Marie-Thérèse Abi Warde  5 , Elise Schaefer  8 , Volker M Sc Kittke  1   2 , Yasemin Dincer  9   10 , Matias Wagner  1   2 , Ivana Dzinovic  1   2 , Riccardo Berutti  1   2 , Tatsuharu Sato  11 , Toshihiko Shirakawa  11 , Yasushi Okazaki  12 , Kei Murayama  4   12 , Konrad Oexle  1   2 , Holger Prokisch  1   2 , Volker Mall  9   13 , Ivo Melčák  14 , Juliane Winkelmann  1   2   15   16 , Michael Zech  1   2
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Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

Philip Harrer et al. Ann Neurol. 2023 Feb.

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.

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References

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