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

Ginevra Zanni, P De Magistris, M Nardella, E Bellacchio, S Barresi, A Sferra, A Ciolfi, M Motta, H Lue, D Moreno-Andres, M Tartaglia, E Bertini, Wolfram Antonin

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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.

Original languageEnglish
JournalCerebellum
DOIs
Publication statusE-pub ahead of print - Feb 11 2019

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Nuclear Pore Complex Proteins
Ataxia
Nuclear Pore
Exome
Nuclear Envelope
Nephrotic Syndrome
Atrophy
Vertebrates
Cytoplasm
Proteins
Steroids
Genes

Cite this

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title = "Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia",
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.",
author = "Ginevra Zanni and {De Magistris}, P and M Nardella and E Bellacchio and S Barresi and A Sferra and A Ciolfi and M Motta and H Lue and D Moreno-Andres and M Tartaglia and E Bertini and Wolfram Antonin",
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doi = "10.1007/s12311-019-1010-5",
language = "English",
journal = "Cerebellum",
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TY - JOUR

T1 - Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia

AU - Zanni, Ginevra

AU - De Magistris, P

AU - Nardella, M

AU - Bellacchio, E

AU - Barresi, S

AU - Sferra, A

AU - Ciolfi, A

AU - Motta, M

AU - Lue, H

AU - Moreno-Andres, D

AU - Tartaglia, M

AU - Bertini, E

AU - Antonin, Wolfram

PY - 2019/2/11

Y1 - 2019/2/11

N2 - 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.

AB - 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.

U2 - 10.1007/s12311-019-1010-5

DO - 10.1007/s12311-019-1010-5

M3 - Article

JO - Cerebellum

JF - Cerebellum

SN - 1473-4222

ER -