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Gain of glycosylation: A new pathomechanism of myelin protein zero mutations
Author(s) -
Prada Valeria,
Passalacqua Mario,
Bono Maria,
Luzzi Paola,
Scazzola Sara,
Nobbio Lucilla Alessandra,
Capponi Simona,
Bellone Emilia,
Mandich Paola,
Mancardi Gianluigi,
Shy Michael,
Sche Angelo,
Grandis Marina
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22695
Subject(s) - missense mutation , glycosylation , myelin , mutant , mutation , mutant protein , phenotype , biology , golgi apparatus , genetics , neuroscience , central nervous system , gene , endoplasmic reticulum
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. Ann Neurol 2012;71:–