Is the carboxyl‐terminus of dystrophin required for membrane association? A novel, severe case of duchenne muscular dystrophy
Author(s) -
Hoffman Eric P.,
Garcia Carlos A.,
Chamberlain Jeffrey S.,
Angelini Corrado,
Lupski James R.,
Fenwick Raymond
Publication year - 1991
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410300414
Subject(s) - dystrophin , duchenne muscular dystrophy , utrophin , muscular dystrophy , itga7 , biology , genetics , microbiology and biotechnology , medicine
Abstract Duchenne muscular dystrophy is a lethal X‐linked recessive disorder caused by the deficiency of a component of the muscle fiber membrane cytoskeleton called dystrophin . Becker muscular dystrophy, a clinically milder disorder, results from dystrophin abnormalities rather than deficiency. We identified the first patient who is clearly an exception to these established clinical and biochemical correlates. The patient described clinically had particularly severe Duchenne dystrophy. Biochemically, his muscle contained substantial amounts of abnormal dystrophin (Becker‐like). Characterization of the dystrophin protein and gene revealed a unique intragenic gene deletion resulting in a dystrophin protein missing the carboxyl‐terminal domain. This patient's dystrophin seemed to have a deleterious “dominant” effect on his muscle: The presence of this abnormal protein was more damaging to the myofibers than the absence of dystrophin would have been. This patient challenges the current hypothesis that dystrophin associates with the plasma membrane solely via its carboxyl‐terminus, yet supports the hypothesis that an intact carboxyl‐terminus is crucial for correct dystrophin function.
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