Av. Winnard et al., CHARACTERIZATION OF TRANSLATIONAL FRAME EXCEPTION PATIENTS IN DUCHENNE BECKER MUSCULAR-DYSTROPHY, Human molecular genetics, 2(6), 1993, pp. 737-744
The clinical progression of Duchenne muscular dystrophy (DMD) patients
with deletions can be predicted in 93% of cases by whether the deleti
on maintains or disrupts the translational reading frame (frameshift h
ypothesis). We have identified and studied a number of patients who ha
ve deletions that do not conform to the translational frame hypothesis
. The most common exception to the frameshift hypothesis is the deleti
on of exons 3 to 7 which disrupts the translational reading frame. We
identified a Becker muscular dystrophy (BMD) patient, an intermediate,
and a DMD patient with this deletion. In all three cases, dystrophin
was detected and localized to the membrane. One DMD patient with an in
frame deletion of exons 4-18 produced no dystrophin. One patient with
a mild intermediate phenotype and a deletion of exon 45, which shifts
the reading frame, produced no dystrophin. Two patients with large inf
rame deletions had discordant phenotypes (exons 3-41, DMD; exons 13-48
, BMD), but both produced dystrophin that localized to the sarcolemma.
The DMD patient, 113, indicates that dystrophin with an intact carbox
y terminus can be produced in Duchenne patients at levels equivalent t
o some Beckers. The dystrophin analysis from these patients, together
with patients reported in the literature, indicate that more than one
domain can localize dystrophin to the sarcolemma. Lastely, the data sh
ows that although most patients show correlation of clinical severity
to molecular data, there are rare patients which do not conform.