An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

“…The most influential determining factor of whether a mutation preserves the function of these critical regions is whether the mutation results in a shift of the transcript reading frame. In large measure, in-frame deletions result in BMD and out-offrame deletions result in DMD (Monaco, 1988). However, there are exceptions to this 'reading frame rule.'…”

Long-term expression of full-length human dystrophin in transgenic mdx mice expressing internally deleted human dystrophins

“…A linear regression curve of the number of manually counted CD8 þ cells versus the pixel area they occupy in the microscopic field was obtained for each experiment (r 2 ¼ 0.81-0.95). For each sample, the average number of CD8 þ cells per random field was extrapolated from the standard curve and expressed as the number of CD8 þ cells per mm 2 . The results are presented as the increased number of CD8 þ cells in the treated muscle compared to the untreated muscle, thus demonstrating possible specific increases above the endogenous CD8 þ counts in dystrophic muscle.…”

“…This is caused by mutations in the dystrophin gene that alter the open-reading frame of dystrophin. 2 The 427 kDa skeletal form of dystrophin has 3685 amino-acid residues and contains several domains: the amino-terminus domain that binds cytoskeletal actin filaments, a large rod-shaped domain formed by 24 repeat sequences that are predicted to adopt a triple helical conformation with four hinges and a carboxyl-terminus domain that binds a whole complex of dystrophin-associated proteins at the sarcolemma. 3 By binding to b-dystroglycan at the membrane, dystrophin acts as a physical link between the cytoskeleton and the extracellular matrix.…”

“…An allelic form of this disease, Becker muscular dystrophy (BMD), is associated with an internally deleted dystrophin molecule due to mutations that maintain the reading frame. 2 This milder form of dystrophy is characterized by a later onset and a slower progression of muscle degeneration.…”

DNA analysis of Duchenne and Becker muscular dystrophy using pERT87 genomic probes and dystrophin cDNA probes

“…Becker muscular dystrophy (BMD) is a less severe form of DMD, and develops signs in the thirties or later; its incidence is one-fifth to one-eighth of that of DMD. Both of these dystrophies have been elucidated to be caused by a common mutation consisting of deletion or duplication of exons within the dystrophin gene (Kingston et al, 1983;Kunkel et al, 1986;Monaco et al, 1988). Because DMD/BMD are still incurable, determining the carrier status and affected fetuses would be very useful for at-risk mothers or relatives whose family members are affected with DMD/BMD from the point of view of genetic counseling.…”