Dystrophin in frameshift deletion patients with Becker muscular dystrophy.
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.
Gangopadhyay
S B
SB
Genetics Department, Hospital for Sick Children, Toronto, Ontario, Canada.
Sherratt
T G
TG
Heckmatt
J Z
JZ
Dubowitz
V
V
Miller
G
G
Shokeir
M
M
Ray
P N
PN
Strong
P N
PN
Worton
R G
RG
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
D016189:Dystrophin; D009838:Oligodeoxyribonucleotides