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.