title: Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule.
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.
authors.affiliation: Leiden University Medical Center, Department of Human Genetics, P.O. Box 9600, 2300 RC Leiden, The Netherlands. a.m.rus@lumc.nl
authors.forename: Annemieke
authors.initials: A
authors.lastname: Aartsma-Rus
authors.forename: Judith C T
authors.initials: JC
authors.lastname: Van Deutekom
authors.forename: Ivo F
authors.initials: IF
authors.lastname: Fokkema
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: Van Ommen
authors.forename: Johan T
authors.initials: JT
authors.lastname: Den Dunnen
mesh_terms: 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*