Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/145276
Author(s): | Santos, M Damásio, J Kun-Rodrigues, C Barbot, C Sequeiros, J Brás, J Alonso, I Guerreiro, R |
Title: | Novel mag variant causes cerebellar ataxia with oculomotor apraxia: Molecular basis and expanded clinical phenotype |
Publisher: | MDPI |
Issue Date: | 2020 |
Abstract: | 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. |
Subject: | Cerebellar ataxia Exome sequencing Myelin-associated glycoprotein |
URI: | https://hdl.handle.net/10216/145276 |
Source: | Journal of Clinical Medicine, vol.9(4):1212 |
Related Information: | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04293%2F2020/PT info:eu-repo/grantAgreement/FCT/3599-PPCDT/FCT-ANR%2FBEX-GMG%2F0008%2F2013/PT info:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBPD%2F116046%2F2016/PT |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | openAccess |
License: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
Files in This Item:
File | Description | Size | Format | |
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10.3390-jcm9041212.pdf | 2.36 MB | Adobe PDF | View/Open |
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