Abstract

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. MostMPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZmutations. Differing phenotypes may reflect the effect of particular mutations on MPZstructure 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, becoming symptomatic only after 30 years. All affected family members were heterozygous for a novel MPZ mutation (Ile99Thr), in a conserved residue.

CONCLUSIONS This broadens the range of familial neuropathy associated with MPZ mutations to include steroid responsive neuropathy, initially diagnosed as chronic inflammatory demyelinating polyneuropathy.