INTEGRATED STUDY OF 100 PATIENTS WITH XP21 LINKED MUSCULAR-DYSTROPHY USING CLINICAL, GENETIC, IMMUNOCHEMICAL, AND HISTOPATHOLOGICAL DATA .1. TRENDS ACROSS THE CLINICAL GROUPS

This multidisciplinary study was undertaken to record the variation in gene and protein expression in a large cohort of patients with well d efined clinical phenotypes. The patients, whose ages ranged from 4 yea rs to 66 years, spanned a wide range of disease severity. They represe nted the first 100 patients who had been examined in Newcastle, had un dergone a muscle biopsy, and provided a blood sample for DNA analysis. The study had three aims: to observe any trends in the analyses acros s the clinical groups, to correlate gene and protein expression in ind ividual patients, and to use the data collected to assess the relative usefulness of different techniques in the diagnosis and prognosis of patients with Duchenne and Becker dystrophy (DMD/BMD). In part 1, we d escribe the clinical assessment of the patients and the trends that we re observed across the cohort. The patients were divided into seven gr oups. Group 1 had severe DMD (n = 21), group 2 had milder DMD (n = 20) , group 3 were intermediate D/BMD patients (n = 9), group 4 had severe BMD (n = 5), and group 5 were more typical BMD patients (n = 31). Som e patients were too young to be classified (n = 7) and a group of all the female patients were also classified separately (n = 7). The numbe r of DMD and BMD patients was about equal, in accord with disease prev alence in the north of England, but an unusually high proportion were sporadic cases. Dystrophin labelling (performed with up to three antib odies) on both blots and sections increased gradually across the clini cal groups. All histopathological indices, except the proportion of fa t in biopsy sections, showed clear trends across the groups.