ARTICLES fibers positive for the developmental myosin heavy chain, a regeneration marker, in LGMD2A was 10% that determined in Duchenne muscular dystrophy (Table). Although apoptosis is not considered essential in the pathophysiology of most muscular dystrophies, and as this had not been determined for LGMD2A, we used TUNEL staining on deltoid muscle biopsies from a variety of muscular dystrophy patients, healthy individuals and a fetus specimen. There was a very low level of myonuclear apoptosis in biopsies of patients affected with Becker muscular dystrophy, Duchenne muscular dystrophy and α-and γ-sarcoglycanopathies (0.0071%±0.0049%, n= 8), whereas none was found in patients affected with Miyoshi myopathy or facio-scapulo-humeral dystrophy or in healthy individuals (Table). However, in the former group of biopsies, most apoptotic features were seen outside the myofiber, presumably in mononuclear cellular infiltrates, as shown by appropriate image merging with the respective phase contrast field or dystrophin immunolabeling (Fig. 2, A23 and A26). In contrast, deltoid sections from 13 LGMD2A patients had 0.40%±0.16% apoptotic myonuclei (Fig. 2, A3 and A4, and Table). Mononuclear cells in LGMD2A interstitial muscular tissue were also found to be TUNEL-positive. However, apoptotic myonuclei were detected mainly in LGMD2A fibers with a microscopic normal morphological appearance (Fig. 2). The staining was typically confined either to isolated nuclei or to a cluster of neighboring myofibers; other areas remained unstained (Fig. 2, A3 and A4). These apoptotic patches were seen in all LGMD2A patients. In serial cross-sections, TUNEL-positive and-negative myonuclei were present in the same fiber, indicating that an individual myonucleus can undergo apoptosis independently of neighboring nuclei (Fig. 3). Myoapoptosis in LGMD2A was con-