title: A severe muscular dystrophy patient with an internally deleted very short (110 kD) dystrophin: presence of the binding site for dystrophin-associated glycoprotein (DAG) may not be enough for physiological function of dystrophin.
abstract: We report a 4-yr and 5-month-old boy with severe clinical features of an early-onset Duchenne muscular dystrophy, who had a very short (110 kDa) dystrophin at the sarcolemma. The patient had a large deletion (exons 2-44) of the dystrophin gene which was predicted to cause a reading frame shift. Sequence analysis of dystrophin mRNA in muscle revealed an alternatively spliced gene product from exons 1 to 51 that caused restoration of the reading frame, in addition to an mRNA corresponding to the DNA deletion. A consistent result was obtained by immunocytochemical analysis of muscle; i.e. positive staining for dystrophin at the sarcolemma using antibodies against the C-terminus, cysteine-rich region and last three of 24 repeat units of the central rod-domain, but not for the remaining antibodies for dystrophin that recognize the N-terminal and proximal rod-domains. Immunostaining for dystrophin-associated glycoproteins (DAGs: 43 and 50 K) and merosin were preserved. Utrophin staining was positive but fainter than other DMD muscles. These results suggest that an extremely short dystrophin lacking the entire actin-binding site in the N-terminus cannot function properly even if the protein possesses the putative DAG-binding cysteine-rich and the C-terminal domains, and still has an ability to associate with sarcolemmal membrane.
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D049030:Dystroglycans; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009132:Muscles / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D049030:Dystroglycans; D004247:DNA