[Severe childhood autosomal recessive muscular dystrophy].
Dystrophin is associated with several novel sarcolemmal proteins via the cysteine-rich/C-terminal domains. The dystrophin-associated proteins are classified into three groups: (1) alpha- and beta-dystroglycan, (2) adhalin, 35DAG and A3b, and (3) members of the syntrophin family. Dystrophin interacts with F-actin via the N-terminal domain. Alpha-dystroglycan binds laminin-2, a major component of the basal lamina. These findings indicate that the dystrophin-glycoprotein complex (DGC) links the subsarcolemmal cytoskeleton with the basal lamina, thus providing mechanical stability to the sarcolemmal. The DGC may also play a role in signal transduction. We have reported previously the deficiency of adhalin in skeletal muscle of Arab patients afflicted with severe childhood autosomal recessive muscular dystrophy (SCARMD). SCARMD is now known to affect other races including Europeans and Japanese. Although the phenotype of this disease can mimic Duchenne muscular dystrophy in severe cases, it is sometimes quite mild. SCARMD is genetically heterogeneous. Recently, adhalin gene mutations have been demonstrated in European, Arab and Japanese families with SCARMD. Another locus is on chromosome 13q, however, the mutated gene remains elusive. In the advanced stages of SCARMD, the expression of laminin is disturbed, suggesting that adhalin deficiency may cause the dysfunction of the DGC as a laminin receptor, which may eventually lead to muscle cell death.
Matsumura
K
K
Department of Neurology and Neuroscience, Teikyo University School of Medicine.
Shimizu
T
T
D017668:Age of Onset; D001485:Basement Membrane; D002648:Child; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D049030:Dystroglycans; D005808:Genes, Recessive; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009136:Muscular Dystrophies / Q000209:etiology*; D009154:Mutation; D017474:Receptors, Laminin / Q000502:physiology; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D017474:Receptors, Laminin; D049031:Sarcoglycans; D049030:Dystroglycans