DELETIONAL DYSTROPHIN GENE MUTATIONS IN MUSCULAR DYSTROPHY IN EGYPT

Abstract

DMD is the most common X-linked disorder in man affecting 1/3,300 live male births. Our understanding of D/BMD has progressed in remarkable leaps in recent years. The identification of the DMD gene and its product, dystrophin has given us substantial new insights into the basic defect in this disease. The discovery of the responsible gene and protein has been referred to as the "end of the beginning". Let us hope that dystrophin research, coupled with studies to evaluate therapeutic approaches will mark the beginning of the end.

When the family history is negative for DMD and BMD (sporadic), the Western blot analysis for protein derived from the molecular biopsy specimen can confinn the clinical diagnosis of D/BMD and can be used to predict the severity of the disease. If the dystrophin assay results is abnormal, DNA analysis should be performed, preferably by PCR and then by Southern blot if PCR failed to detect a deletion. Detection of a dystrophin gene deletion or duplication will greatly facilitate carrier detection and prenatal diagnosis in the proband's family. However, failure of the diagnosis of D/BMD, in the event that no deletion or duplication is found, RFLPs linkage analysis can be attempted for prenatal diagnosis and detection of carriers. When muscle biopsy specimen is not available, or if the severity of the disease is predictable or apparent at presentation, PCR or Southern blot testing of peripheral blood DNA can be informative in more than 60% to 65% of the cases.