Duchenne/Becker
Duchenne/Becker Muscular Dystrophy Deletion Detection
Duchenne and Becker muscular dystrophies (DMD and BMD) are progressive neuromuscular disorders caused by mutations in the dystrophin gene at Xp21. The more severe Duchenne is the result of absence of detectable dystrophin while the milder Becker results when a partially functional protein is still being produced. DMD affects approximately 1 in 3,500 male births.
Clinical features: DMD most commonly presents in early childhood with the inability to run normally and a tendency to walk on the toes.
It can occasionally present at birth as hypotonia or later as failure to thrive or delayed walking. The most distinct clinical features are progressive proximal muscular dysfunction and pseudohypertrophy of the calves. Although the cardiac muscle is involved, death in most boys is primarily the result of respiratory problems. The onset is usually before 3 years, with wheelchair dependency by age 12 and death in the late teens or 20s. The onset of BMD is often in the 20s or 30s and survival to a relatively advanced age is common.
Inheritance: X-linked recessive. A carrier female has a 25% chance to have an affected son with each pregnancy (50% chance the child is a boy and a 50% chance the boy is affected). Each daughter of a carrier female has a 50% chance to be a carrier herself. However, approximately 1/4 of DMD cases are thought to be the result of new mutation. Gonadal mosaicism is also known to exist in DMD/BMD, further complicating risk assessment in families with a single affected male.
Mutation information: Deletions in the dystrophin gene are detected in approximately 60-65% of affected individuals and duplications are about 5%. These deletions and duplications, can be detected by polymerase chain reaction (PCR) using five sets of primers specific for exons within the dystrophin gene and MLPA. Since approximately 30% of affected males having point mutations will have point mutation, a negative deletion or duplications result does not rule out DMD or BMD. Detection of point mutations is required full sequencing of the gene.
Indications and benefits: Testing may be considered in males with suspicious clinical symptoms. The assay is designed to confirm the clinical diagnosis of Duchenne or Becker Muscular Dystrophy in males. It is not be able to test heterozygous carriers (females). If a deletion is identified in an affected male, prenatal diagnosis of DMD/BMD is available for male fetuses in future at risk pregnancies in the family.
Test methodology: Multiplex polymerase chain reaction assay is used to test a total of 32 exons of the dystrophin gene, which will detect 98% of deletions in the dystrophin gene. The accuracy of this assay is felt to exceed 99%. The MLPA and sequencing of the gene also used for deletion, duplication and point mutations analysis of DMD/BMD gene.
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