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Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia

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A Correction to this article was published on 05 March 2019

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Abstract

Nuclear pore complexes (NPCs) are the gateways of the nuclear envelope mediating transport between cytoplasm and nucleus. They form huge complexes of 125 MDa in vertebrates and consist of about 30 different nucleoporins present in multiple copies in each complex. Here, we describe pathogenic variants in the nucleoporin 93 (NUP93) associated with an autosomal recessive form of congenital ataxia. Two rare compound heterozygous variants of NUP93 were identified by whole exome sequencing in two brothers with isolated cerebellar atrophy: one missense variant (p.R537W) results in a protein which does not localize to NPCs and cannot functionally replace the wild type protein, whereas the variant (p.F699L) apparently supports NPC assembly. In addition to its recently described pathological role in steroid-resistant nephrotic syndrome, our work identifies NUP93 as a candidate gene for non-progressive congenital ataxia.

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  • 05 March 2019

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Acknowledgements

The authors thank the patients and their family for their participation in this study.

Funding

This work was supported by grants from the Italian Ministry of Health (Ricerca Finalizzata NET-2013-02356160 to E.B), Fondazione Bambino Gesù (Vite Coraggiose to M.T), and the German Research Foundation to W.A (AN377/7-1).

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Authors and Affiliations

  1. Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, IRCCS, 00146, Rome, Italy

    Ginevra Zanni, M. Nardella, A. Sferra & E. Bertini

  2. Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, 52074, Aachen, Germany

    P. De Magistris, H. Lue, D. Moreno-Andres & Wolfram Antonin

  3. Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy

    E. Bellacchio, S. Barresi, A. Ciolfi, M. Motta & M. Tartaglia

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  1. Ginevra Zanni
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Contributions

Conceived and designed the project: GZ and WA. Performed the experiments: PDM, MN, EB, SB, AS, AC, MM, HL, and DMA. Analyzed the data: GZ, WA, EB, and MT. Contributed to the writing of the manuscript: GZ and WA. All authors approved the final version of this manuscript.

Corresponding authors

Correspondence to Ginevra Zanni or Wolfram Antonin.

Ethics declarations

All studies were performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participating subjects.

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The authors declare that they have no competing interests.

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The original version of this article was revised: The western blot presented in Figure b shows white lines has been corrected. Also the ESM3 was replaced.

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Zanni, G., De Magistris, P., Nardella, M. et al. Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia. Cerebellum 18, 422–432 (2019). https://doi.org/10.1007/s12311-019-1010-5

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