G.P.76 Dystrophin levels do not influence disease progression in Becker muscular dystrophy patients with an exon 45–47 deletion

Abstract

Becker Muscular Dystrophy (BMD) shows a highly variable disease course. The cause of this diversity is mostly unknown. Dystrophin levels in muscle tissue are thought to be an important factor. We investigated the relationship between the amount of dystrophin in muscle biopsies and clinical severity in BMD patients with an exon 45–47 deletion. Thirteen patients with an exon 45–47 deletion were included, ranging in age from 20 to 63years. Muscle strength was bilaterally measured using the Quantitative Muscle Testing (QMT) system in nine muscle groups: shoulder abduction, elbow flexion/extension, handgrip, hip flexion/extension, knee flexion/extension and ankle flexion. To assess muscle quality 3T MRI of the lower leg was performed. A muscle biopsy was taken from the anterior tibial muscle. Dystrophin quantification was performed by Western Blot analysis, using two antibodies: DYS1 (rod domain) and AB15277 (C-terminus). Statistical analysis was performed using Pearson’s correlation test. Dystrophin levels ranged from 15% to 71% compared to healthy control muscle. The correlation between the two antibodies was excellent (R 0.88; p<0.001). No relationship was present between dystrophin levels and QMT-sum score or fatty infiltration on MRI. In contrast, the QMT-sum score and fatty infiltration on MRI correlated significantly with patients’ age. The current study shows that the dystrophin level in itself does not explain the variation in disease severity in BMD patients with an exon 45–47 deletion. The strong relationship between strength or MRI abnormalities and age suggests that in this subgroup of Becker patients the disease course is determined by the mutation rather than the quantity of the internally deleted dystrophin protein.