Phenotypic variability in a Chinese family with rimmed vacuolar distal myopathy.
BACKGROUND
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene mutations have been found in patients with distal myopathy with rimmed vacuoles (DMRV). It is not clear how the same GNE gene mutations can result in different phenotypes in the same family with DMRV.


METHODS
The clinical, neurophysiological, histopathological, and genetic characteristics of two patients with DMRV from a Chinese family from Taiwan were investigated.


RESULTS
Two novel compound heterozygous mutations in different domains of the protein, Ile241Ser in the epimerase and Trp513stop in the kinase domain, were detected in both patients. However, the two patients demonstrated different patterns of disease progression: one had slow disease progression with a typical feature of DMRV (that is, weakness beginning in the distal leg muscles, typically anterior tibialis, with the quadriceps remaining relatively unaffected), and the other had rapid disease progression with an atypical presentation of DMRV.


CONCLUSIONS
The results of the present study indicate that GNE gene mutations and probably modifier gene(s) or additional factors may result in different phenotypes of DMRV.
Ro
L-S
LS
Department of Neurology, Chang Gung Memorial Hospital, 199 Tun Hwa North Road, Taipei, Taiwan 10591.
Lee-Chen
G-J
GJ
Wu
Y-R
YR
Lee
M
M
Hsu
P-Y
PY
Chen
C-M
CM
D000328:Adult; D002681:China; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014617:Vacuoles / Q000473:pathology*
D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase