Dystrophin in Frameshift Deletion Patients with Becker Muscular Dystrophy

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1992 Sep 1

PMID 1496988

Citations 23

Authors

S B Gangopadhyay

T G Sherratt

J Z Heckmatt

V Dubowitz

G Miller

M Shokeir

P N Ray

P N Strong

R G Worton

Affiliations

Soon will be listed here.

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.

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