ABSTRACT
Duchenne muscular dystrophy (DMD) and the milder phenotype, Becker muscular dystrophy (BMD), are allelic X-linked disorders characterized by progressive, degenerative myopathy (1). About 95% of the DMD patients are diagnosed before the age of six, whereas BMD patients may show variable phenotypes with symptoms ranging from less severe DMD-like to very mild in patients who remain ambulant throughout their lives. The first diagnostic test used in patients suspected of DMD is the measurement of serum creatine kinase (CK) levels. Markedly elevated serum CK activities are observed in both DMD and BMD patients (1). Muscle biopsies of these patients will then be examined (immuno)histochemically. In parallel with, or before immunological muscle analysis, genetic studies are used to confirm the clinical diagnosis in the index patient and to further investigate their families for carrier status, and in prenatal diagnosis. In the majority of patients, one or more exons are deleted (60%) or duplicated (6%) (2-5). These rearrangements are patient-specific and unevenly distributed. In most of the remaining DMD patients, nonsense, frameshift, and frameshifting
SECTION II: DIAGNOSTIC CONSIDERATIONS
splice site mutations are found to be the causative mutations. For the detection of these small mutations, various DNA-based techniques and RNAbased methods, such as the protein truncation test (PTT), which uses mRNA isolated from lymphocytes, frozen muscle sections (preferably), or MyoD-differentiated fibroblasts, are available (6,7). Additional reverse transcription-polymerase chain reaction (RT-PCR) studies are also performed in case novel mutations are revealed and are predicted to affect splicing. The large size (approximately 2.4Mb) of the dystrophin gene and the high number of exons, 79, make a complete genetic analysis an arduous task.
