DMPK

The DMPK gene provides instructions for making a protein called myotonic dystrophy protein kinase. Although the exact function of this protein is not known, it appears to be important for the normal function of muscle, heart, and brain cells. This protein may be involved in communication within cells. It also appears to regulate the production and function of important structures inside muscle cells. For example, myotonic dystrophy protein kinase has been shown to turn off (inhibit) a specific subunit (PPP1R12A) of a muscle protein called myosin phosphatase. Myosin phosphatase is an enzyme that plays a role in muscle tensing (contraction) and relaxation. Myotonic dystrophy protein kinase may interact with other proteins as well.

One region of the DMPK gene has a particular repeating sequence of three DNA building blocks (nucleotides), written as CTG. The CTG sequence is usually repeated 5 to 35 times within the gene and is called a trinucleotide repeat.

myotonic dystrophy - caused by mutations in the DMPK gene

Type 1 myotonic dystrophy is caused by an expansion of the CTG trinucleotide repeat in the DMPK gene. This condition occurs when the CTG segment is abnormally repeated from 50 to 5,000 times. The mutated DMPK gene produces an altered version of messenger RNA, which is a molecular blueprint of the gene that is normally used for protein production. Researchers have found that the altered messenger RNA interacts with certain proteins to form clumps within the cell. The abnormal clumps interfere with the production of many other proteins. These changes prevent cells in muscles and other tissues from functioning properly, leading to the signs and symptoms of type 1 myotonic dystrophy.

The size of the abnormally expanded CTG repeat is associated with the severity of signs and symptoms. People with the classic features of type 1 myotonic dystrophy, including muscle weakness and wasting beginning in adulthood, usually have 100 to 1,000 CTG repeats. People born with the more severe congenital form of type 1 myotonic dystrophy tend to have a larger number of CTG repeats, often more than 2,000. This form of the condition is apparent in infancy and may involve life-threatening medical problems.

As the altered DMPK gene is passed from one generation to the next, the size of the CTG repeat expansion often increases in size. People with 35 to 49 CTG repeats have not been reported to develop type 1 myotonic dystrophy, but their children are at risk of having the disorder if the number of CTG repeats increases. Repeat lengths from 35 to 49 are called premutations.