title: Deficiency of syntrophin, dystroglycan, and merosin in a female infant with a congenital muscular dystrophy phenotype lacking cysteine-rich and C-terminal domains of dystrophin.
abstract: Primary deficiency of merosin is the cause of the classic form of congenital muscular dystrophy (CMD) accompanied by brain white matter abnormalities. We report a female infant with dystrophinopathy who was deficient in merosin in skeletal muscle. The patient had a phenotype of typical CMD and white matter abnormalities on brain MRI. Merosin was greatly reduced in the biopsied skeletal muscle. However, the expression of dystroglycan and syntrophin was also greatly reduced, and the immunoreactivity for the antibodies against the cysteine-rich/C-terminal domains of dystrophin was absent in the sarcolemma. Reverse transcriptase polymerase chain reaction analysis of the dystrophin gene revealed a complete lack of exons 71 through 74. In skeletal muscle, only the mutant gene was expressed. These results suggest that the patient is a symptomatic Duchenne muscular dystrophy carrier with skewed X-inactivation. This patient illustrates for the first time that a dystrophin abnormality can cause a secondary deficiency of merosin in dystrophinopathy. The reduction of merosin may account for the clinical phenotype of CMD and correlate with the white matter abnormalities in our patient.
authors.affiliation: School of Health Sciences, Sapporo Medical University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tachi
authors.forename: K
authors.initials: K
authors.lastname: Ohya
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.forename: S Y
authors.initials: SY
authors.lastname: Patria
authors.forename: K
authors.initials: K
authors.lastname: Matsumura
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins / Q000172:deficiency*; D049030:Dystroglycans; D016189:Dystrophin / Q000235:genetics*; D049029:Dystrophin-Associated Proteins; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000172:deficiency*; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000172:deficiency*; D008565:Membrane Proteins / Q000172:deficiency; D009124:Muscle Proteins / Q000172:deficiency*; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C091824:syntrophin; C091825:syntrophin alpha1; D049030:Dystroglycans