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Gain of glycosylation: a new pathomechanism of myelin protein zero mutations
Valeria Prada1, Mario Passalacqua, Maria Bono
1Department of Neurosciences, Ophthalmology, and Genetics, University of Genoa, Genoa, Italy.
Abstract:
We report the first case of a missense mutation in MPZ causing a gain of glycosylation in myelin protein zero, the main protein of peripheral nervous system myelin. The patient was affected by a severe demyelinating neuropathy caused by a missense mutation, D32N, that created a new glycosylation sequence. We confirmed that the mutant protein is hyperglycosylated, is partially retained into the Golgi apparatus in vitro, and disrupts intercellular adhesion. By sequential experiments, we demonstrated that hyperglycosylation is the main mechanism of this mutation. Gain of glycosylation is a new mechanism in Charcot-Marie-Tooth type 1B.
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