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Fig. 1 Schematic description of the exon structure of the dystrophin gene. The dystrophin gene consisting of 79 exons (boxes) and at least eight alternative promoters (boxes under the lined boxes) is schematically described. Numbers over the box indicate exon number, the bold numbers being the exons that are examined by multiplex PCR. Quadrilaterals and parallelograms indicate in-frame exons (type 0 exons). Trapezoids indicate out-of-frame exons (type 1 or type 2 exons).

Fig. 1 Schematic description of the exon structure of the dystrophin gene. The dystrophin gene consisting of 79 exons (boxes) and at least eight alternative promoters (boxes under the lined boxes) is schematically described. Numbers over the box indicate exon number, the bold numbers being the exons that are examined by multiplex PCR. Quadrilaterals and parallelograms indicate in-frame exons (type 0 exons). Trapezoids indicate out-of-frame exons (type 1 or type 2 exons).

premature stop codon is created. This rule predicts that milder BMD patients would produce a smaller semifunctional protein whereas DMD patients would either produce a severely truncated dystrophin lacking the entire C-terminal region or would not produce dystrophin at all.

Subsequent gene analyses have shown that over 90% of the deletion-duplication mutations that cause BMD maintain the dystrophin mRNA reading frame whereas those causing DMD are frameshifts.[9] Accordingly, point mutations identified in DMD are nonsense mutations[10] except in rare DMD cases with missense mutations.[11,12]

Considering that molecular therapy for DMD to change the reading frame from out-of-frame to in-frame has been proposed,[13,14] it is important to see the resulting translational reading frame of dystrophin mRNA after the identification of a deletion or duplication mutation. Exons of the dystrophin gene are classified into three types according to the number of nucleotides encoded in the exon (Fig. 1): 1) in-frame exon that encodes nucleotides of multiples of 3 (type 0 exon); 2) two out-of-frame exons that have nucleotides of multiples of 3 +1 or 2 (type 1 exon or type 2 exon, respectively). Among the 79 exons, 40, 18, and 21 exons are classified into types 0, 1, and 2 exons, respectively. In cases with deletion/ duplication of the dystrophin gene the reading frame can be determined as described in Fig. 1. Cases having a deletion of a type 2 exon, e.g., exon 45, should be DMD based on the reading frame rule. Although gene diagnosis of DMD/BMD has been conducted, not all DMD/BMD cases have been examined for its reading frame.

In other types of mutations, nonsense mutations are expected to be identified in DMD. However, nonsense mutation that should result in DMD phenotype has been identified in BMD cases,[8,15] where exon skipping is shown as a mechanism that modified clinical phenotype. Furthermore, BMD has been shown to have a nonsense mutation in in-frame exons.[16-18] Detailed analysis of genotype-phenotype correlation would lead a better understanding of molecular mechanism of dystrophinopathy.

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Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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