[Molecular genetics and problems found in genetic diagnosis of Duchenne Becker muscular dystrophy]

Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are the most common inherited muscular diseases and caused by mutations in the dystrophin gene. Half to two-thirds of DMD and BMD patients carry deletions (usually of several kilobases of genomic DNA). The clinical progression in DMD and BMD patients with deletions can be predicted in 92% of cases based on whether the deletion maintains or disrupts the translational reading frame (frame-shift hypothesis). However, some exceptional cases have been reported; BMD cases whose dystrophin gene exons 3 to 7 were deleted (out-of-frame), more severe case whose dystrophin gene deletion maintains reading frame but includes N-terminal region, and so on. Splicing mutation is one kind of mutations of dystrophin gene, and usually induced by small mutation of exon-intron boundary sequence. However, intraexonal small mutation also induces exon skipping, due to disruption of exon recognition sequence, which is intraexonal sequence and necessary for splicing of the upstream intron. For molecular diagnosis of DMD/BMD it is important to analyze not only in genomic DNA level, but also in mRNA, protein, and clinical levels. And the relationship between molecular abnormality and clinical phenotype should be examined, especially when extramuscular symptoms (heart failure and mental retardation) are prominent.