Like other X-linked traits, most cases of DMD are inherited by sons from their maternal parents. X-linked disorders arise from a mutation in the X-chromosome thus even a single altered copy would result into the expression of the disorder in males since they possess only one X-chromosome. In females, however, having two X-chromosomes means that X-linked disorders such as DMD only result from mutations on both copies. Where a mutation occurs on one copy in females however, such females could act as carriers and pass on the disorder to their sons.
Due to such association with the X-chromosome, most cases of DMD are noted to arise from inheritance. For instance, two thirds of DMD cases have been attributed in a thesis to inheritance from maternal carriers (Bestard, 2000, p. 10). However, apart from inheritance, the thesis also attributes one third of the DMD to de novo spontaneous mutations (Bestard 2000, p. 10). Such spontaneous mutations are possibly a consequence of the huge size of the implicated gene – the dystrophin gene - and its possession of regions susceptible to deletions.
Mutation Prone Regions in Dystrophin Gene
The regions prone to mutations in dystrophin gene comprise important exons (functionally silent regions) required for the transcription process. According to a review of therapeutics in DMD, by affecting these exons, mainly exons 45 and 55, the mutations alter the reading frame thus preventing the transcription process from taking place (Strober, 2006). The review further advances that most mutations arise from single or multiple deletions (60% of the boys) with duplication accounting for a smaller percentage [5%] (Strober, 2006, p.230). The remainder of the cases according to this review arises from point mutations – a type of mutation that involves a single base replacement in the nucleotide DNA sequence.
Similar DMD forms could however arise out of different sizes (single versus multiple) and different positions of the alterations. Such forms from varying antecedents have been postulated in the thesis to result from a shift in the reading frame (Bestard, 2000). Variants of muscular dystrophies can also be explained by the impact of mutations on the gene expression process. Depending on the effect of these mutations muscular dystrophies could range from mild to serious forms.
When the mutations lead to a shift in the reading frame preventing transcription initiation, the review advances that the absence of the ultimate product of the gene’s expression -Dystrophin protein - results into the Duchenne form (phenotype) disorder. However; when the mutations do not disrupt the reading frame thus allowing transcription and translation, but with the ultimate product being a defective protein, it is noted that a milder form of the disorder - the Becker Muscular Dystrophy (BMD) manifests (Strober, 2006).
References:
Bestard, J. (2000). Dystrophin gene regulation in the muscle. tspace.library.utoronto.ca (accessed February 09, 2010)
Strober, J.B. (2006). Therapeutics in Duchenne muscular Dystrophy. NeuroRx, 3, 225-234. journals.elsevierhealth.com (accessed February 09, 2010)
Geoffrey Miriti - Msc (biostatistics) Bsc. (Biochemistry) Certified Public Accountant (CPA) Research assistant in a biotechnology firm Project ...
Join the Conversation