ABNORMAL DYSTROPHIN EXPRESSION IN PATIENTS WITH LIMB-GIRDLE SYNDROMES

Clinical differential diagnosis between Becker muscular dystrophy (BMD ) and limb gridle muscular dystrophy (LGMD) may be difficult because t he BMD clinical phenotype tends to overlap with other limb girdle synd romes, especially with LGMD. Therefore we studied the expression of dy strophin, the protein product of the Becker and Duchenne muscular dyst rophy gene, in muscle biopsy specimens of 30 patients (18 males, of wh om 15 represented spradic cases, and 12 females) diagnosed as having L GMD according to traditional clinical, electrophysiological and histol ogical criteria. For dystrophin analysis, six different monoclonal ant ibodies directed against different epitopes of the dystrophin molecule were used. Immunocytochemically, five of the 30 LGMD patients (17%) s howed abnormal dystrophin staining patterns diagnostic of BMD. Western blotting in these five patients, all sporadic cases, showed dystrophi n of reduced size and/or abundance. Analysis of blood or muscle DNA us ing multiplex polymerase chain reaction revealed deletions in the dyst rophin gene in three of the five. Thus, 5 of 15 (33%) sporadic male pa tients previously thought to have LGMD were identified as having BMD.