Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation

摘要

OBJECTIVE—To report anovel hereditary motor and sensory neuropathy (HMSN) phenotype, withpartial steroid responsiveness, caused by a novel dominant mutation inthe myelin protein zero (MPZ) gene. MostMPZ mutations lead to the HMSN type Iphenotype, with recent reports of Déjérine-Sottas, congenitalhypomyelination, and HMSN II also ascribed to MPZmutations. Differing phenotypes may reflect the effect ofparticular mutations on MPZstructure and adhesivity.
METHODS—Clinical,neurophysiological, neuropathological, and molecular genetic analysisof a family presenting with an unusual hereditary neuropathy.
RESULTS—Progressivedisabling weakness, with positive sensory phenomena and areflexia,occurred in the proband with raised CSF protein and initial steroidresponsiveness. Nerve biopsy in a less severely affected siblingdisclosed a demyelinating process with disruption of compacted myelin.The younger generation were so far less severely affected, becomingsymptomatic only after 30 years. All affected family members wereheterozygous for a novel MPZ mutation(Ile99Thr), in a conserved residue.
CONCLUSIONS—Thisbroadens the range of familial neuropathy associatedwith MPZ mutations to include steroidresponsive neuropathy, initially diagnosed as chronic inflammatorydemyelinating polyneuropathy.