Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule.
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.
Aartsma-Rus
Annemieke
A
Leiden University Medical Center, Department of Human Genetics, P.O. Box 9600, 2300 RC Leiden, The Netherlands. a.m.rus@lumc.nl
Van Deutekom
Judith C T
JC
Fokkema
Ivo F
IF
Van Ommen
Gert-Jan B
GJ
Den Dunnen
Johan T
JT
D030541:Databases, Genetic; D005787:Gene Frequency; D005858:Germany; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016364:Reading Frames / Q000235:genetics*