INTEGRATED STUDY OF 100 PATIENTS WITH XP21 LINKED MUSCULAR-DYSTROPHY USING CLINICAL, GENETIC, IMMUNOCHEMICAL, AND HISTOPATHOLOGICAL DATA .3. DIFFERENTIAL-DIAGNOSIS AND PROGNOSIS

This report is the third part of a trilogy from a multidisciplinary st udy which was undertaken to investigate gene and protein expression in a large cohort of patients with well defined and diverse clinical phe notypes. The aim of part 3 was to review which of the analytical techn iques that we had used would be the most useful for differential diagn osis, and which would provide the most accurate indication of disease severity. Careful clinical appraisal is very important and every DMD p atient was correctly diagnosed on this basis. In contrast, half of the sporadic BMD patients and all of the sporadic female patients had rec eived different tentative diagnoses based on clinical assessments alon e. Sequential observations of quantitative parameters (such as the tim e taken to run a fixed distance) were found to be useful clinical indi cators for prognosis. Intellectual problems might modify the impressio n of physical ability in patients presenting at a young age. Histopath ological assessment was accurate for DMD but differentiation between B MD and other disorders was more difficult, as was the identification o f manifesting carriers. Our data on a small number of women with sympt oms of muscle disease indicate that abnormal patterns of dystrophin la belling on sections may be an effective way of differentiating between female patients with a form of limb girdle dystrophy and those carryi ng a defective Xp21 gene. Dystrophin gene analysis detects deletions/d uplications in 50 to 90% of male patients and is the most effective no n-invasive technique for diagnosis. Quantitative Western blotting, how ever, would differentiate between all Xp21 and non-Xp21 male patients. In this study we found a clear relationship between increased dystrop hin abundance (determined by densitometric analysis of blots) and clin ical condition, with a correlation between dystrophin abundance and th e age at loss of independent mobility among boys with DMD and intermed iate D/BMD. This indicates that blotting is the most sensitive and acc urate technique for diagnosis and prognosis.