CHARACTERIZATION OF TRANSLATIONAL FRAME EXCEPTION PATIENTS IN DUCHENNE BECKER MUSCULAR-DYSTROPHY

被引:82
作者
WINNARD, AV
KLEIN, CJ
COOVERT, DD
PRIOR, T
PAPP, A
SNYDER, P
BULMAN, DE
RAY, PN
MCANDREW, P
KING, W
MOXLEY, RT
MENDELL, JR
BURGHES, AHM
机构
[1] OHIO STATE UNIV, DEPT NEUROL,1654 UPHAM DR,452 MEANS HALL,ROOM 452, COLUMBUS, OH 43210 USA
[2] HOSP SICK CHILDREN, DEPT GENET, TORONTO M5G 1X8, ONTARIO, CANADA
[3] UNIV ROCHESTER, DEPT NEUROL, ROCHESTER, NY 14620 USA
[4] STRONG MEM HOSP, ROCHESTER, NY 14642 USA
[5] OHIO STATE UNIV, DEPT MED BIOCHEM, COLUMBUS, OH 43210 USA
[6] OHIO STATE UNIV, COLL MED, DEPT PATHOL, COLUMBUS, OH 43210 USA
[7] OHIO STATE UNIV, COLL BIOL SCI, DEPT MOLEC GENET, COLUMBUS, OH 43210 USA
关键词
D O I
10.1093/hmg/2.6.737
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The clinical progression of Duchenne muscular dystrophy (DMD) patients with deletions can be predicted in 93% of cases by whether the deletion maintains or disrupts the translational reading frame (frameshift hypothesis). We have identified and studied a number of patients who have deletions that do not conform to the translational frame hypothesis. The most common exception to the frameshift hypothesis is the deletion 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 inframe 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 inframe 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 carboxy terminus can be produced in Duchenne patients at levels equivalent to 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 shows that although most patients show correlation of clinical severity to molecular data, there are rare patients which do not conform.
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页码:737 / 744
页数:8
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