Concomitant deficiency of β- and γ-sarcoglycans in 20 α-sarcoglycan (adhalin)-deficient patients: immunohistochemical analysis and clinical aspects

Abstract

We have investigated the expression, using immunohistochemistry, of β- and γ-sarcoglycans in the muscles of 20 patients in whom previous screening had revealed a deficiency of α-sarcoglycan. α-, β- and γ-sarcoglycans were absent in 7 patients and variably reduced in 8 patients, in 2 of whom β-sarcoglycan was more reduced than the α- and γ-proteins. In 5 other patients with variably reduced α- and β-sarcoglycans, γ-sarcoglycan was completely absent. In all patients the distribution of hyposthenia at disease onset was similar, and predominantly involved pelvic girdle muscles; however, the age at onset and rate of disease progression were highly variable. In severely compromised patients, the onset of disease was before 10 years of age and γ-sarcoglycan or all three sarcoglycans were absent from muscles. Immunohistochemical analysis of sarcoglycans should be part of routine screening for muscle dystrophies to identify patients with sarcoglycanopathy. Gene analysis is necessary to identify the primary defect; however, sarcoglycan immunohistochemistry may be useful for indicating which gene to investigate. Further biochemical characterization of the interactions between these proteins is required to fully elucidate their roles in causing severe, moderate or mild muscular dystrophy.