Myotonic dystrophy type 1 (MD1) is a form of muscular dystrophy that is caused by a mutation in the dystrophia myotonica protein kinase, or DMPK gene, found on chromosome 19.

The disease is inherited in an autosomal dominant pattern, which means that a single copy of the mutated gene, inherited from one parent, is enough to cause MD1. In other words, the children of a person with MD1 have a 50 percent chance of inheriting it.

Mutation in the DMPK gene

The mutation in the DMPK gene that leads to MD1 is a trinucleotide repeat expansion. This means that three nucleotides (or letters in the DNA) — in this case, CTG — are repeated too many times, much like a skipping record. A normal DMPK gene has 3 to 37 repetitions of the CTG sequence; in MD1, there are hundreds to thousands of repetitions of this sequence.

As the mutated DMPK gene is copied and passed down generations, the number of CTG repeats tends to increase, a phenomenon known as genetic anticipation. This is significant because MD1 symptoms generally appear earlier, and are more severe, in patients with higher numbers of CTG repeats. So as the disease is passed down through a family, children who inherit it may be affected at younger ages and have increasingly severe symptoms.

What the mutation does

The DNA sequence in a gene is essentially a code that gives instructions for making a specific protein. When the cell needs to make the protein, the DNA is transcribed into molecules called RNA that are then sent to the structures in a cell that synthesize proteins. When a DMPK gene with too many CTG repeats is transcribed, the resulting RNA is too long. This abnormally long RNA is toxic to cells.

The extra-long RNA forms clumps and tangles inside the cell. It is thought that these tangles can ensnare and disable other proteins that are essential for a cell to work normally. The resulting cellular dysfunction leads to the symptoms of MD1.

Understanding exactly how the CTG repeats in the DMPK gene cause the symptoms seen in MD1 may help scientists develop better ways to treat the disease at its source. For instance, researchers are working on techniques to break up toxic RNA tangles or to prevent proteins from getting trapped in them.

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