In frame and out of frame deletions

Some of us had been asking what these terms mean so when in April I had my yearly visit to see my consultant I asked him what these meant. I hope I have not missed out anything or mistyped anything so please excuse me if I have.

“These are technical terms describing the type of mutation leads to conditions like Becker Muscular Dystrophty. As you are aware BMD is caused by a fault( that is a mutation) in the Dystrophin gene.

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 howether 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

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Becker Index.htm