Dystrophin content in muscle was analyzed by both immunofluorescence and immunoblot in 41 patients with a clinical diagnosis of limb-girdle muscular dystrophy seen at the National Institute of Neuroscience, Tokyo, Japan over a 12-year period. 17% showed a dystrophinopathy consistent with Becker (5 male patients) or carrier of Duchenne (2 female patients) muscular dystrophy. The misclassification of isolated male patients was 31 % while that of isolated female patients was 13%. DNA analysis confirmed a dystrophin gene deletion in all five male Becker dystrophy patients identified. By analysis of this study together with two additional reports in the literature, the authors calculate that approximately 40% of isolated limb-girdle/Becker patients cannot be differentially diagnosed on the basis of clinical and histopathologic criteria. Dystrophin protein and gene studies are required for the accurate diagnosis of these patients and before appropriate genetic counseling can be provided. [1]

COMMENT. The study demonstrates the clinical overlap between limb-girdle muscular dystrophy and dystrophinopathies and emphasizes the necessity of dystrophin protein and gene studies for accurate diagnosis of isolated cases of muscular dystrophy.

Hoffman, EP et al, from the University of Pittsburgh School of Medicine, describe a novel, severe case of Duchenne muscular dystrophy with biochemical findings that were consistent with a Becker muscular dystrophy. The muscle contained substantial amounts of abnormal dystrophin and a unique intragenic gene deletion resulting in a dystrophin protein missing the carboxyl-terminal domain. This abnormal protein was more damaging to the myofibers than the absence of dystrophin would have been and supports the hypothesis that an intact carboxyl-terminus is crucial for correct dystrophin function. Previous studies have suggested that the carboxyl-terminus of dystrophin is important for normal dystrophin function. The patient described here had dystrophin that lacked the carboxyl-terminus domain yet it was clearly associated with the plasma membrane. [2]

Matsumura K et al, from the Department of Neurology, Shimoshizu National Hospital, Chiba, Tokyo, Japan, describe a Japanese family with both Fukuyama type congenital muscular dystrophy and Duchenne muscular dystrophy [3]. DNA analysis and the dystrophin test showed that dystrophin was expressed normally at the sarcoplasmic membrane of the Fukuyama phenotype patient but was completely absent in the Duchenne phenotype patient. Two different childhood muscular dystrophies coexisted in this family. The dystrophin test assisted in the differential diagnosis of the two diseases when DNA analysis by Southern blotting was not informative.