Background and purpose: Duchenne/Becker muscular dystrophies (DMD/BMD) lead to progressive irreversible muscle deterioration caused by recessive mutations in the dystrophin encoding gene (Xp21.1). Approximately 60% of mutations are deletions, 10% are duplications and the remaining 30% are point mutations. The aim of the study is to present the rare occurrence of two pathogenic mutations (deletions or duplications) in one allele of the dystrophin gene.
Material and methods: DNA of patients from 1364 DMD/ BMD families was tested. Two techniques - PCR-multiplex and multiplex ligation-dependent probe amplification - were used to search for mutations in the dystrophin gene.
Results: Deletion was detected in 648 families and duplication was found in 74 families (analysis in progress). In two families, presence of two mutations in one gene was documented - in the first family two deletions were found (exons 45-49 and 60-61), and in the second family two duplications were detected (exons 2-7 and 50-59). One of the deletions disrupted the reading frame, and the other deletion retained the reading frame. Both duplications also retained the reading frame of the gene but in both families the disease took a severe course (DMD). In the family with two duplications prenatal diagnosis was also carried out, and carriership of both mutations was discovered in the female fetus.
Conclusions: In the analyzed group of DMD/BMD families, the frequency of combined occurrence of two mutations in one gene was 2 per 722 (0.3%). The phenomenon of detected non-contiguous deletions and duplications is presented together with 31 similar cases published so far.