title: Dystrophin in frameshift deletion patients with Becker muscular dystrophy.
abstract: In a previous study we identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. We have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases we detected slightly lower-molecular-weight dystrophin in 12%-15% abudance relative to the normal. By sequencing amplified mRNA we have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternative splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame.
authors.affiliation: Genetics Department, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: S B
authors.initials: SB
authors.lastname: Gangopadhyay
authors.forename: T G
authors.initials: TG
authors.lastname: Sherratt
authors.forename: J Z
authors.initials: JZ
authors.lastname: Heckmatt
authors.forename: V
authors.initials: V
authors.lastname: Dubowitz
authors.forename: G
authors.initials: G
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Shokeir
authors.forename: P N
authors.initials: PN
authors.lastname: Ray
authors.forename: P N
authors.initials: PN
authors.lastname: Strong
authors.forename: R G
authors.initials: RG
authors.lastname: Worton
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D016189:Dystrophin / Q000032:analysis / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: D016189:Dystrophin; D009838:Oligodeoxyribonucleotides