Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation.
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, 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.
Donaghy
M
M
Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK. Joanne.Wilkinson@clineuro.ox.ac.uk
Sisodiya
S M
SM
Kennett
R
R
McDonald
B
B
Haites
N
N
Bell
C
C
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018993:Myelin P0 Protein / Q000235:genetics*; D009431:Neural Conduction; D010375:Pedigree; D011115:Polyneuropathies / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013256:Steroids / Q000627:therapeutic use*
D018993:Myelin P0 Protein; D013256:Steroids