OBJECTIVE—To report a novel hereditary motor and sensory neuropathy (HMSN) phenotype, with partial steroid responsiveness, caused by a novel dominant mutation in the myelin protein zero (MPZ) gene. Most MPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZ mutations. Differing phenotypes may reflect the effect of particular mutations on MPZ structure and adhesivity. METHODS—Clinical, neurophysiological, neuropathological, and molecular genetic analysis of a family presenting with an unusual hereditary neuropathy. RESULTS—Progressive disabling weakness, with positive sensory phenomena and areflexia, occurred in the proband with raised CSF protein and initial steroid responsiveness. Nerve biopsy in a less severely affected sibling disclosed 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.
