This case demonstrates that an out-of-frame exon 45 deletion can induce exon 44 skipping to produce dystrophin, though the resulting conformational change may still lead to a severe Duchenne muscular dystrophy phenotype.
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Severe DMD phenotype persists despite dystrophin from exon 44 skipping; leaves open conformational determinants of severity in exon deletions.
The exon 45 deletion is a common dystrophin gene deletion. Although this is an out-of-frame deletion, which should not allow for protein synthesis, it has been observed in mildly affected patients. We describe a patient with an exon 45 deletion who produced protein, but still had a severe Duchenne muscular dystrophy phenotype. RT-PCR analysis and cDNA sequencing from the muscle biopsy sample revealed that the exon 45 deletion induced exon skipping of exon 44, which resulted in an in-frame deletion and the production of dystrophin. A conformational change in dystrophin induced by the deletion is proposed as being responsible for the severe phenotype in the patient. We feel that the variable clinical phenotype observed in patients with the exon 45 deletion is not due to exon splicing but may be the result of other environmental or genetic factors, or both.
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Prior et al. (1997) studied this question.
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