Pathogenesis (disease development)
Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease affecting the DMD gene.
More than 80% of the cases are caused by Raster mutations (= deletions (loss of nucleobases), insertions (additional insertion of nucleobases) or duplications (duplication of nucleobases)), which lead to a protein with a significantly altered structure, making it non-functional. Non-sense mutations (point mutation in the DNA sequence leading to a stop codon) occur in 10-15% of cases, causing translation (translation into protein) to be aborted prematurely and also resulting in a protein that is significantly altered in structure and thus defective. The remaining percent are primarily missense mutations (meaning-changing mutations: Point mutation that causes the incorporation of another amino acid into the protein) – in this case, the protein is only slightly altered in its structure and thus only partially restricted in function.
If, despite the corresponding mutation, a residual protein is still present, this is referred to as Becker-Kiener muscular dystrophy (similar symptomatic course, but in a weakened form).
If no distrophin protein exists, the actin filaments of the cell cannot establish a connection to the glycoprotein beta-dystroglycan, which thus cannot bind to the protein alpha-dystroglycan located in the extracellular space.
If a muscle contraction now takes place, the cell is considerably damaged in its stability and structure. The cell membrane therefore dissolves in some places. The enzyme creatine kinase (CK; synonyms: creatine kinase; creatine phosphokinase (CPK); creatine phosphokinase (KPK), adenosine-5′-triphosphate-creatinine-phosphotransferase), which is essential for the energy metabolism of the cell, now diffuses into the extracellular space and calcium ions enter the cell. Eventually, death (lysis) of a cell occurs.
The adult of the described symptoms of DMD now results from muscle tissue being replaced by fat as well as connective tissue.
Etiology (Causes)
Biographic causes
