Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy.
BACKGROUND
Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE).


OBJECTIVE
To determine whether DMRV and HIBM are allelic.


METHODS
The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured.


RESULTS
The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity.


CONCLUSIONS
DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.
Nishino
I
I
Department of Neuromuscular Research, National Institute of Neuroscience, Kodaira, Tokyo, Japan. nishino@ncnp.go.jp
Noguchi
S
S
Murayama
K
K
Driss
A
A
Sugie
K
K
Oya
Y
Y
Nagata
T
T
Chida
K
K
Takahashi
T
T
Takusa
Y
Y
Ohi
T
T
Nishimiya
J
J
Sunohara
N
N
Ciafaloni
E
E
Kawai
M
M
Aoki
M
M
Nonaka
I
I
D000483:Alleles; D002238:Carbohydrate Epimerases / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D029968:Escherichia coli Proteins; D008040:Genetic Linkage / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D018979:Myositis, Inclusion Body / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D014617:Vacuoles / Q000648:ultrastructure
D029968:Escherichia coli Proteins; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; C083982:wecB protein, E coli