Novel Myelin Protein Zero Mutation in 3 Generations of Vermonters With Demyelinating Charcot–Marie–Tooth Disease

Conclusions:The novel MPZ base-pair substitution in this family is associated with inherited distal demyelinating neuropathy and should be reclassified as pathogenic for Charcot–Marie–Tooth.
Objectives:
We report the clinical phenotype in 3 consecutive generations with demyelinating Charcot–Marie–Tooth disease that possess a novel sequence variant of myelin protein zero (MPZ).
Methods:
Family members from 3 consecutive generations were interviewed, examined, and studied with electrodiagnostic testing. Commercially available next-generation sequencing was performed for the proband. Single-gene analysis was performed for the remaining family members.
Results:
All patients demonstrated symmetric distal weakness; symmetric distal sensory loss; and diminished deep tendon reflexes. Electrodiagnostic testing was consistent with primary distal demyelination with secondary axon loss. Genetic testing identified a novel base-pair substitution of MPZ (c.314C>T), resulting in a missense variant (p.Pro105Leu).
Conclusions:
The novel MPZ base-pair substitution in this family is associated with inherited distal demyelinating neuropathy and should be reclassified as pathogenic for Charcot–Marie–Tooth.

Source: Journal of Clinical Neuromuscular Disease - February 22, 2018 Category: Neurology Tags: Original Article Source Type: research