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Open AccessArticle

Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype

1
UnIGENe, IBMC-Institute for Molecular and Cell Biology, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
2
CGPP, IBMC-Institute for Molecular and Cell Biology, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
3
Neurology Department, Centro Hospitalar do Porto, 4099-001 Porto, Portugal
4
Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, Michigan, MI 49503, USA
5
Division of Psychiatry and Behavioral Medicine, Michigan State University College of Human Medicine, Grand Rapids, Michigan, MI 49503, USA
*
Authors to whom correspondence should be addressed.
Present address: Genetyca-ICM, 4100-134 Porto, Portugal.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(4), 1212; https://doi.org/10.3390/jcm9041212
Received: 2 April 2020 / Revised: 17 April 2020 / Accepted: 19 April 2020 / Published: 23 April 2020
(This article belongs to the Section Molecular Diagnostics)
Homozygous variants in MAG, encoding myelin-associated glycoprotein (MAG), have been associated with complicated forms of hereditary spastic paraplegia (HSP). MAG is a glycoprotein member of the immunoglobulin superfamily, expressed by myelination cells. In this study, we identified a novel homozygous missense variant in MAG (c.124T>C; p.Cys42Arg) in a Portuguese family with early-onset autosomal recessive cerebellar ataxia with neuropathy and oculomotor apraxia. We used homozygosity mapping and exome sequencing to identify the MAG variant, and cellular studies to confirm its detrimental effect. Our results showed that this variant reduces protein stability and impairs the post-translational processing (N-linked glycosylation) and subcellular localization of MAG, thereby associating a loss of protein function with the phenotype. Therefore, MAG variants should be considered in the diagnosis of hereditary cerebellar ataxia with oculomotor apraxia, in addition to spastic paraplegia. View Full-Text
Keywords: cerebellar ataxia; myelin-associated glycoprotein; exome sequencing cerebellar ataxia; myelin-associated glycoprotein; exome sequencing
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MDPI and ACS Style

Santos, M.; Damásio, J.; Kun-Rodrigues, C.; Barbot, C.; Sequeiros, J.; Brás, J.; Alonso, I.; Guerreiro, R. Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype. J. Clin. Med. 2020, 9, 1212. https://doi.org/10.3390/jcm9041212

AMA Style

Santos M, Damásio J, Kun-Rodrigues C, Barbot C, Sequeiros J, Brás J, Alonso I, Guerreiro R. Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype. Journal of Clinical Medicine. 2020; 9(4):1212. https://doi.org/10.3390/jcm9041212

Chicago/Turabian Style

Santos, Mariana; Damásio, Joana; Kun-Rodrigues, Célia; Barbot, Clara; Sequeiros, Jorge; Brás, José; Alonso, Isabel; Guerreiro, Rita. 2020. "Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype" J. Clin. Med. 9, no. 4: 1212. https://doi.org/10.3390/jcm9041212

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