Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.
BACKGROUND
Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder characterized by severe dystrophic muscle wasting from birth or early infancy with structural brain abnormalities. The gene for FCMD is located on chromosome 9q31, and encodes a novel protein named fukutin. The function of fukutin is not known yet, but is suggested to be an enzyme that modifies the cell-surface glycoprotein or glycolipids.


OBJECTIVE
To elucidate the roles of fukutin gene mutation in skeletal and cardiac muscles and brain.


METHODS
Immunohistochemical and immunoblot analyses were performed in skeletal and cardiac muscles and brain tissue samples from patients with FCMD and control subjects.


RESULTS
The authors found a selective deficiency of highly glycosylated alpha-dystroglycan, but not beta-dystroglycan, on the surface membrane of skeletal and cardiac muscle fibers in patients with FCMD. Immunoblot analyses also showed no immunoreactive band for alpha-dystroglycan, but were positive for beta-dystroglycan in FCMD in skeletal and cardiac muscles.


CONCLUSIONS
The current findings suggest a critical role for fukutin gene mutation in the loss or modification of glycosylation of the extracellular peripheral membrane protein, alpha-dystroglycan, which may cause a crucial disruption of the transmembranous molecular linkage of muscle fibers in patients with FCMD.
Hayashi
Y K
YK
Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, Japan. hayasi_y@ncnp.go.jp
Ogawa
M
M
Tagawa
K
K
Noguchi
S
S
Ishihara
T
T
Nonaka
I
I
Arahata
K
K
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000378:metabolism; D049030:Dystroglycans; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D008565:Membrane Proteins; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics* / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; C113587:FKTN protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D049030:Dystroglycans