Molecular genetic research on the peculiar form of Becker Muscular Dystrophy (BMD), where cardiac muscle is preferentially involved

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Cardiac muscle was preferentially involved in some patients of BMD,and we found the deletion of the DMD gene around intron 1 in these patients. We started further study based on the hypothesis that preferential cardiac involvement was due to aberrant transcriptional regulation of the DMD gene.1) Incidence of the BMD families with cardiac involvement in JapanWe investigated the incidence of BMD families with cardiac involvement in Japan in collaboration with Department of Medicine in Shinsyu University. BMD patients with cardiac involvement who have the deletion between exon 45-48 of the DMD gene, showed typical skeletal muscle symptom for BMD.However the group of BMD patients with cardiac involvement, who revealed the deletion around the 5'-end of the DMD gene, often developed cardiac involvement without overt skeletal muscle symptom.2) Analysis of the DMD gene of BMD family with cardiac involevementWe collected the BMD families, which show preferential cardiac involvement and the deletion around 5'-end of the gene. The molecular genetic study using DNA marker for intron 1 of the gene revealed that preferential cardiac involvement cannot be explained by the deletion of the particular part of the intron 1.3) Transcriptional regulation of the DMD gene in cardiac muscleWe prepared the series of constructions which contain various lengths of the DMD gene promoter with CAT reporter gene. We transfected these constructs into the C2 cells or rat neonatal primary cardiac cells. The promoter construct, which has up to-102bp of the gene showed the highest activities in skeletal and cardiac cells. The fragment contained the CArG box sequence and the deletion or the mutation of the CArG box sequence leads the loss of activities in both cells.