Phenotypic and genomic characterization of Becker dystrophy patients with 45 to 55 exons deletion

Becker muscular dystrophy (BMD) is an X linked disorder with 1/30000 life births incidence and is characterized by a progressive muscular dystrophy with or without cardiomyopathy. We present a population of 49 BMD patients with a DMD gene in-phase deletion of exons 45 to 55 (BMDdel45-55). Interestingly, emerging regulatory actors as lncRNA are localized in introns 44 and 55 (Bovolenta et al., 2012). Thus, the specific neo-introns of each patient could create or modify the lncRNA and/or RNA non-coding sequences. The objective of this study is to identify modifier factors involved in phenotypic variability in BMDdel45-55 patients. As described in literature, 63% of Duchenne patients are eligible to a multiexon skipping therapy by skipping exons 45 to 55.We performed (i) a phenotypic characterization of 49 patients, (ii) a lncRNA profile in 40/49patients and (iii) a WGS in 19/49patients. We have established the profile of lncRNA presence at genomic level in healthy subjects, muscle biopsies of BMDdel45-55 and DMD patients and human immortalized myoblasts displaying a deletion of 45-52 exons in DMD gene (Myo-45-52).In our cohort 22% of patients have dilatative cardiomyopathy, interestingly in 51% the first signs age was