ABSENCE OF CORRELATION BETWEEN UTROPHIN LOCALIZATION AND QUANTITY ANDTHE CLINICAL SEVERITY IN DUCHENNE BECKER DYSTROPHIES/

While present in the surface membrane of embryonic muscle fibers, in a dult normal muscle fibers, utrophin is restricted to the motor endplat e and cells of blood vessel walls, However, the observation that utrop hin is maintained in the extrajunctional plasma membrane in Duchenne ( DMD) and in mdx muscle fibers has led to the suggestion that excess ut rophin might compensate for dystrophin deficiency in the Xp21 muscular dystrophies, In order to detect an inverse correlation of utrophin pr esence and clinical severity, we have assessed utrophin distribution a nd quantity in DMD and Becker (BMD) patients of different ages and sta ges of clinical severity, All patients showed a positive discontinuous immunolabeling of utrophin on the sarcolemma, staining equally small and large muscle fibers, indicating that immature characteristics are maintained in such fibers, On Western blot, utrophin bands with concen trations 2- to 10-fold greater than in normal controls were detected i n all DMD/BMD patients, However, no negative correlation was found bet ween the amount of utrophin and the severity of clinical course, imply ing that the detectable utrophin levels in these patients did not comp ensate for dystrophin deficiency, In a DMD patient with growth hormone (GH) deficiency and a BMD-like clinical course, utrophin levels were comparable to the other typical DMD cases, which reinforces the hypoth esis that the observed increase in utrophin is apparently not responsi ble for a milder clinical course in some patients with Xp21 muscular d ystrophies. (C) 1995 Wiley-Liss, Inc.