Selective deficiency of α-dystroglycan in Fukuyama-type congenital muscular dystrophy

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Abstract
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 α-dystroglycan, but not β-dystroglycan, on the surface membrane of skeletal and cardiac muscle fibers in patients with FCMD. Immunoblot analyses also showed no immunoreactive band for α-dystroglycan, but were positive for β-dystroglycan in FCMD in skeletal and cardiac muscles. Conclusion: The current findings suggest a critical role for fukutin gene mutation in the loss or modification of glycosylation of the extracellular peripheral membrane protein, α-dystroglycan, which may cause a crucial disruption of the transmembranous molecular linkage of muscle fibers in patients with FCMD.