What Causes it?

A fault in the gene (carried on the X chromosome) which is used to manufacture a protein called dystrophin leads to the formation of a faulty protein in muscle fibres. In Duchenne muscular dystrophy this protein is missing or severely abnormal but in Becker muscular dystrophy a milder fault leads to a lack of  dystrophin than normal. Because of this lack of dystrophin the muscle fibres gradually break down and this causes the muscles to slowly become weaker.

“The fault results in a change in the genetic material contained within the dystrophin gene. This fault can take a variety of forms.

The dystrophin gene is made up of a chain of chemicals . These constitute the “genetic code”., which gives the instruction for the manufacture in the body of the normal dystrophin protein. When the gene is affected by a mutation , normal protein cannot be produced and this results in muscular dystrophy.

In BMD the commonest mutations are deletions of the dystrophin gene. In these a chunk of the gene has been missed out. This means that the genetic code is incomplete and the dystophin protein that is produced is abnormal. The deletions can be described as either being “in frame” or “out of frame” .To understand this you need to understand the way that the genetic code works. Basically it is a string of chemicals arranged in groups of 3. The groups of 3 are called codons, each codon gives a specific instruction for the assembly of the dystrophin protein.

If a deletion occurs which takes out a whole number of codons (say 2 or 6) this is refered to as an inframe deletion. This means the genetic code can still be read in sequence, if simply the part of it is missing. If the deletion takes out part of a codon then it is said to be out of frame. This is because the genetic message no longer can be read beyond the point of the mutation. Out of frame deletions tend to be associated with worse problems with manufacture of dystophin, and with worse forms of muscular dystrophy. However this relationship is not reliable.

I hope an example will help you to understand more easily. If you think of the codons as words , they can spell out a sentence (the complete sentence corresponds to the normal dystrophin protein).

For example: The fat cat ate the wee rat.

You can see that if a single word is deleted the sentence can still make some sense but part of it is missing.

For example: The fat cat ate the rat.

If however a deletion occurs which takes out a bit of a word instead of a whole word, the words (which have to remain in groups of 3) beyond the deletion no longer make sense.

For Example : The fat cat ate the eer at.

As you can see the 2^nd “mutation” which is out of frame makes the last 2 words nonsensical. In the 1^st example , the “in frame” mutation, a small part of the sentence is missing and it can still to some extent be understood.

I hope this is helpful.

Dr J. Nixon

Consultant Neurologist

“

The above description provided by my consultant covers cases where some of the code is missing this is known as Deletions but sometimes the mutation is a duplication .In the case of duplications the code is repeated and can result in a genetic disorder through the disruption of exon organisation. One way I can explain the cause of Becker is to compare DNA to a computer program which has become corrupted and does not function 100% .