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

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.