From dystrophinopathy to sarcoglycanopathy: Evolution of a concept of muscular dystrophy

Abstract

Duchenne and Becker muscular dystrophies are collectively termed dystrophinopathy. Dystrophinopathy and severe childhood autosomal recessive muscular dystrophy (SCARMD) are clinically very similar and had not been distinguished in the early 20th century. SCARMD was first classified separately from dystrophinopathy due to differences in the mode of inheritance. Studies performed several years ago clarified some immunohistochemical and genetic characteristics of SCARMD, but many remained to be clarified. In 1994, the sarcoglycan complex was discovered among dystrophin‐associated proteins. Subsequently, on the basis of our immunohistochemical findings which indicated that all components of the sarcoglycan complex are absent in SCARMD muscles, and the previous genetic findings, we proposed that a mutation of any one of the sarcoglycan genes leads to SCARMD. This hypothesis explained and predicted various characteristics of SCARMD at the molecular level, most of which have been verified by subsequent discoveries in our own as well as various other laboratories. SCARMD is now called sarcoglycanopathy, which is caused by a defect of any one of four different sarcoglycan genes, and thus far mutations in sarcoglycan genes have been documented in the SCARMD patients. In this review, the evolution of the concept of sarcoglycanopathy separate from that of dystrophinopathy is explained by comparing studies on these diseases. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:421–438, 1998.

Sarcoglycanopathy: Clinical and histochemical characteristics in 66 patients

“…SGP is unique in that in principle the four muscular dystrophies belonging to this group are indistinguishable not only in terms of clinical features but also in terms of immunohistochemical examination of the muscles. [45,46] Genetic studies are necessary for discriminating individual SGPs as the same phenotype results from the mutation of various genes. Unfortunately, we were unable to perform genetic analysis on our patients.…”

Distal myopathies: clinical and molecular diagnosis and classification

“…It will be interesting to see in the future whether the proteins mutated in these and the other distal myopathies interact, just as so many of the proteins mutated or missing in the muscular dystrophies interact 45. Two-hybrid studies using dysferlin may help identify other distal myopathy genes if this is so.…”

Biomechanics of the sarcolemma and costameres in single skeletal muscle fibers from normal and dystrophin-null mice

“…Defects in proteins at costameres can compromise muscle force production during contraction either directly, by reducing the efficiency of lateral force transmission, or indirectly, by increasing the chances that the sarcolemma will be weakened and damaged, resulting in degeneration or death of the myofiber (Reed and Bloch 2005; Blaauw et al 2008). Many muscular dystrophies, associated with a profound weakness and fragility of myofibers (Barton 2006), have been linked to alterations in costameric proteins such as dystrophin (Hoffman et al 1987; Williams and Bloch 1999b; Rybakova et al 2000; Ervasti 2007), sarcoglycans (Nigro et al 1996; Williams and Bloch 1999a; Lapidos et al 2004), and dystroglycans (Ozawa 1998; Campbell and Stull 2003; Ayalon et al 2008). …”