Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

Philip Harrer; Audrey Schalk; Masaru Shimura; Sarah Baer; Nadège Calmels; Marie Aude Spitz; Marie Thérèse Abi Warde; Elise Schaefer; 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

doi:10.1002/ana.26544

Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

Philip Harrer, Audrey Schalk, Masaru Shimura, Sarah Baer, Nadège Calmels, Marie Aude Spitz, Marie Thérèse Abi Warde, Elise Schaefer, 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 MallIvo Melčák, Juliane Winkelmann, Michael Zech

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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.

Original language	English
Pages (from-to)	330-335
Number of pages	6
Journal	Annals of Neurology
Volume	93
Issue number	2
DOIs	https://doi.org/10.1002/ana.26544
State	Published - Feb 2023

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Harrer, P., Schalk, A., Shimura, M., Baer, S., Calmels, N., Spitz, M. A., Warde, M. T. A., Schaefer, E., Kittke, V. M. S., Dincer, Y., Wagner, M., Dzinovic, I., Berutti, R., Sato, T., Shirakawa, T., Okazaki, Y., Murayama, K., Oexle, K., Prokisch, H., ... Zech, M. (2023). Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions. Annals of Neurology, 93(2), 330-335. https://doi.org/10.1002/ana.26544

@article{19df705ab8154b05a9c03e4cf0ab3d18,

title = "Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions",

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.",

author = "Philip Harrer and Audrey Schalk and Masaru Shimura and Sarah Baer and Nad{\`e}ge Calmels and Spitz, {Marie Aude} and Warde, {Marie Th{\'e}r{\`e}se Abi} and Elise Schaefer and Kittke, {Volker M.Sc} and Yasemin Dincer and Matias Wagner and Ivana Dzinovic and Riccardo Berutti and Tatsuharu Sato and Toshihiko Shirakawa and Yasushi Okazaki and Kei Murayama and Konrad Oexle and Holger Prokisch and Volker Mall and Ivo Mel{\v c}{\'a}k and Juliane Winkelmann and Michael Zech",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2023",

month = feb,

doi = "10.1002/ana.26544",

language = "English",

volume = "93",

pages = "330--335",

journal = "Annals of Neurology",

issn = "0364-5134",

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Harrer, P, Schalk, A, Shimura, M, Baer, S, Calmels, N, Spitz, MA, Warde, MTA, Schaefer, E, Kittke, VMS, Dincer, Y, Wagner, M, Dzinovic, I, Berutti, R, Sato, T, Shirakawa, T, Okazaki, Y, Murayama, K, Oexle, K, Prokisch, H, Mall, V, Melčák, I, Winkelmann, J & Zech, M 2023, 'Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions', Annals of Neurology, vol. 93, no. 2, pp. 330-335. https://doi.org/10.1002/ana.26544

TY - JOUR

T1 - Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

AU - Harrer, Philip

AU - Schalk, Audrey

AU - Shimura, Masaru

AU - Baer, Sarah

AU - Calmels, Nadège

AU - Spitz, Marie Aude

AU - Warde, Marie Thérèse Abi

AU - Schaefer, Elise

AU - Kittke, Volker M.Sc

AU - Dincer, Yasemin

AU - Wagner, Matias

AU - Dzinovic, Ivana

AU - Berutti, Riccardo

AU - Sato, Tatsuharu

AU - Shirakawa, Toshihiko

AU - Okazaki, Yasushi

AU - Murayama, Kei

AU - Oexle, Konrad

AU - Prokisch, Holger

AU - Mall, Volker

AU - Melčák, Ivo

AU - Winkelmann, Juliane

AU - Zech, Michael

PY - 2023/2

Y1 - 2023/2

N2 - 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.

AB - 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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DO - 10.1002/ana.26544

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C2 - 36333996

AN - SCOPUS:85142282659

SN - 0364-5134

VL - 93

SP - 330

EP - 335

JO - Annals of Neurology

JF - Annals of Neurology

IS - 2

ER -

Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions

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