The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.
About 60% of both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) is due to deletions of the dystrophin gene. For cases with a deletion mutation, the "reading frame" hypothesis predicts that BMD patients produce a semifunctional, internally deleted dystrophin protein, whereas DMD patients produce a severely truncated protein that would be unstable. To test the validity of this theory, we analyzed 258 independent deletions at the DMD/BMD locus. The correlation between phenotype and type of deletion mutation is in agreement with the "reading frame" theory in 92% of cases and is of diagnostic and prognostic significance. The distribution and frequency of deletions spanning the entire locus suggests that many "in-frame" deletions of the dystrophin gene are not detected because the individuals bearing them are either asymptomatic or exhibit non-DMD/non-BMD clinical features.
Koenig
M
M
Division of Genetics, Howard Hughes Medical Institute, Children's Hospital, Boston.
Beggs
A H
AH
Moyer
M
M
Scherpf
S
S
Heindrich
K
K
Bettecken
T
T
Meng
G
G
Müller
C R
CR
Lindlöf
M
M
Kaariainen
H
H
de la Chapellet
A
A
Kiuru
A
A
Savontaus
M L
ML
Gilgenkrantz
H
H
Récan
D
D
Chelly
J
J
Kaplan
J C
JC
Covone
A E
AE
Archidiacono
N
N
Romeo
G
G
Liechti-Gailati
S
S
Schneider
V
V
Braga
S
S
Moser
H
H
Darras
B T
BT
Murphy
P
P
Francke
U
U
Chen
J D
JD
Morgan
G
G
Denton
M
M
Greenberg
C R
CR
Wrogemann
K
K
Blonden
L A
LA
van Paassen
M B
MB
van Ommen
G J
GJ
Kunkel
L M
LM
D000293:Adolescent; D002648:Child; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D015342:DNA Probes; D015247:Deoxyribonuclease HindIII; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D006801:Humans; D009136:Muscular Dystrophies / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D016364:Reading Frames; D015183:Restriction Mapping; D014158:Transcription, Genetic
D015342:DNA Probes; D016189:Dystrophin; D015247:Deoxyribonuclease HindIII