DYSTROPHIN CHARACTERIZATION IN BMD PATIENTS - CORRELATION OF ABNORMALPROTEIN WITH CLINICAL PHENOTYPE

We have investigated protein expression and genotype in 59 Becker musc ular dystrophy (BMD) patients. The aim was to identify possible causes of the marked variability in phenotype in patients with similar delet ions/mutations. The patients were examined neurologically and function ally and underwent Manual Muscle Testing. Dystrophin expression was an alysed by immunohistochemistry and western blot using antibodies again st six different segments of the protein. DNA mutations were investiga ted by PCR amplification of 30 exons. Based on dystrophin expression a t the sarcolemma, two groups of patients were identified: group A (29 patients) with the classic patchy distribution of dystrophin and group B (30 patients) with absence or reduction of one or more dystrophin p ortions and variable, although mostly normal, expression of the other portions of the protein. Dystrophin molecular weight was normal or sli ghtly reduced in group A and was variably reduced, generally conspicuo usly so, in group B. The quantity of dystrophin expressed varied marke dly in both groups. The pattern of immunohistochemical staining in gro up B patients correlated with milder clinical phenotype, suggesting th at small dystrophin molecules lacking a portion in the N-terminus or i n the rod domain, are more functional than proteins with normal or sli ghtly reduced molecular weight that display the BMD-typical patchy dis tribution at the sarcolemma.