Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.
Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).
Warner
L E
LE
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Hilz
M J
MJ
Appel
S H
SH
Killian
J M
JM
Kolodry
E H
EH
Karpati
G
G
Carpenter
S
S
Watters
G V
GV
Wheeler
C
C
Witt
D
D
Bodell
A
A
Nelis
E
E
Van Broeckhoven
C
C
Lupski
J R
JR
D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics*; D003001:Cloning, Molecular; D015331:Cohort Studies; D003461:Crystallography; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005838:Genotype; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D018993:Myelin P0 Protein / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000502:physiology; D011487:Protein Conformation; D013497:Sural Nerve / Q000648:ultrastructure
D018993:Myelin P0 Protein