INTEGRATED STUDY OF 100 PATIENTS WITH XP21 LINKED MUSCULAR-DYSTROPHY USING CLINICAL, GENETIC, IMMUNOCHEMICAL, AND HISTOPATHOLOGICAL DATA .2. CORRELATIONS WITHIN INDIVIDUAL PATIENTS

This report is the second part of a trilogy from a multidisciplinary s tudy which was undertaken to record the relationships between clinical severity and dystrophin gene and protein expression. The aim in part 2 was to correlate the effect of gene deletions on protein expression in individual patients with well defined clinical phenotypes. Among th e DMD patients, most of the deletions/duplications disrupted the open reading frame, but three patients had in frame deletions. Some of the intermediate D/BMD patients had mutations which were frameshifting whi le others were in frame. All of the deletions/duplications in the BMD patients maintained the open reading frame and 25/26 deletions in typi cal BMD group 5 started with exon 45. The deletion of single exon 44 w as the most common mutation in patients from groups 1 to 3. Dystrophin was detected in sections and blots from 58% of the DMD patients with a size that was compatible with synthesis from mRNA in which the readi ng frame had been restored. Certain deletions were particularly associ ated with the occurrence of limited dystrophin synthesis in DMD patien ts. For example, 9/11 DMD patients missing single exons had some detec table dystrophin labelling compared with 10/24 who had deletions affec ting more than one exon. All patients missing single exon 44 or 45 had some dystrophin. Deletions starting or finishing with exons 3 or 51 ( 8/9) cases were usually associated with dystrophin synthesis whereas t hose starting or finishing with exons 46 or 52 (11/11) were not. Forma l IQ assessments (verbal, performance, and full scores) were available for 47 patients. Mean IQ score among the DMD patients was 83 and no c lear relationship was found between gene mutations and IQ. The mutatio ns in patients with a particularly severe deficit of verbal IQ were sp read throughout the gene.