Entries in the Leiden Duchenne Muscular Dystrophy Mutation Database: An Overview of Mutation Types and Paradoxical Cases That Confirm the Reading-Frame Rule

Muscle Nerve. 2006 Aug;34(2):135-44. doi: 10.1002/mus.20586.

Abstract

The severe Duchenne and milder Becker muscular dystrophy are both caused by mutations in the DMD gene. This gene codes for dystrophin, a protein important for maintaining the stability of muscle-fiber membranes. In 1988, Monaco and colleagues postulated an explanation for the phenotypic difference between Duchenne and Becker patients in the reading-frame rule: In Duchenne patients, mutations induce a shift in the reading frame leading to prematurely truncated, dysfunctional dystrophins. In Becker patients, in-frame mutations allow the synthesis of internally deleted, but largely functional dystrophins. Currently, over 4700 mutations have been reported in the Leiden DMD mutation database, of which 91% are in agreement with this rule. In this study we provide an update of the mutational variability in the DMD gene, particularly focusing on genotype-phenotype correlations and mutations that appear to be exceptions to the reading-frame rule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Databases, Genetic
  • Gene Frequency
  • Germany
  • Humans
  • Muscular Dystrophy, Duchenne / genetics*
  • Mutation / genetics*
  • Phenotype
  • Reading Frames / genetics*