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- W2793313299 abstract "Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal CaV2.1 function due to aberrant N-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients’ group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show similarities. Hypoglycosylation of both CaV2.1 subunits (α1A and α2α) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N-glycosylation site N283 at α1A contributes to a gain-of-function by lessening CaV2.1 inactivation. Hypoglycosylation of the α2δ subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the CaV2.1 channel. CaV2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant CaV2.1 N-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities." @default.
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- W2793313299 date "2018-02-22" @default.
- W2793313299 modified "2023-10-18" @default.
- W2793313299 title "Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy" @default.
- W2793313299 cites W1603155066 @default.
- W2793313299 cites W1865501820 @default.
- W2793313299 cites W1965020589 @default.
- W2793313299 cites W1966049079 @default.
- W2793313299 cites W1967248338 @default.
- W2793313299 cites W1971247150 @default.
- W2793313299 cites W1974163301 @default.
- W2793313299 cites W1983971650 @default.
- W2793313299 cites W1986788837 @default.
- W2793313299 cites W1988594569 @default.
- W2793313299 cites W1991280665 @default.
- W2793313299 cites W2000655632 @default.
- W2793313299 cites W2003607733 @default.
- W2793313299 cites W2004048072 @default.
- W2793313299 cites W2005913674 @default.
- W2793313299 cites W2009840012 @default.
- W2793313299 cites W2027313746 @default.
- W2793313299 cites W2037453672 @default.
- W2793313299 cites W2044444729 @default.
- W2793313299 cites W2050254109 @default.
- W2793313299 cites W2052328862 @default.
- W2793313299 cites W2055387293 @default.
- W2793313299 cites W2063829584 @default.
- W2793313299 cites W2066080151 @default.
- W2793313299 cites W2069902794 @default.
- W2793313299 cites W2073404613 @default.
- W2793313299 cites W2075295969 @default.
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- W2793313299 cites W2095515981 @default.
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- W2793313299 cites W2130088345 @default.
- W2793313299 cites W2133121644 @default.
- W2793313299 cites W2133566590 @default.
- W2793313299 cites W2145811165 @default.
- W2793313299 cites W2145932431 @default.
- W2793313299 cites W2152681129 @default.
- W2793313299 cites W2158985001 @default.
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- W2793313299 cites W2217461512 @default.
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- W2793313299 cites W2262959984 @default.
- W2793313299 cites W2263771359 @default.
- W2793313299 cites W2398434040 @default.
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- W2793313299 doi "https://doi.org/10.3390/ijms19020619" @default.
- W2793313299 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5855841" @default.
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