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

Lorance, David, K., MD; Mandigo, Kelly, A., RN; Hehir, Michael, K., MD

Journal of Clinical Neuromuscular Disease: March 2018 - Volume 19 - Issue 3 - p 101–107
doi: 10.1097/CND.0000000000000188
Original Article

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.

Charcot–Marie–Tooth disease is a heterogeneous group of inherited neuropathies classified by clinical severity, demyelinating versus axonal electrophysiology, inheritance pattern, and genetic mutation.

Department of Neurological Sciences, University of Vermont, Burlington, VT.

Reprints: David Lorance, MD, University of Vermont Medical Center, Mailstop 351EP5, East Pavilion 5, 111 Colchester Avenue, Burlington, VT 05401 (e-mail: david.lorance@uvmhealth.org).

The authors report no conflicts of interest.

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