期刊
JOURNAL OF CLINICAL MEDICINE
卷 9, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/jcm9041212
关键词
cerebellar ataxia; myelin-associated glycoprotein; exome sequencing
资金
- FCT-Fundacao para a Ciencia e a Tecnologia, I.P. [UIDB/04293/2020]
- FEDER funds through the Programa Operacional Factores de Competitividade-COMPETE 2020
- FCT [FCT-ANR/BEX-GMG/0008/2013, COMPETE: POCI-01-0145-FEDER-007440]
- Porto Neurosciences and Neurologic Disease Research Initiative at the i3S - Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 through FEDER [Norte-01-0145-FEDER-000008]
- i3S Scientific Platform Advanced Light Microscopy [PPBI-POCI-01-0145-FEDER-022122, POCI-01-0145-FEDER-022184]
- FCT - POPH/MCTES [SFRH/BPD/116046/2016]
- Fundação para a Ciência e a Tecnologia [FCT-ANR/BEX-GMG/0008/2013, UIDB/04293/2020] Funding Source: FCT
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.
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