Dystonia 16 – PRKRA gene

Dystonia 16 (DYT16) is one of the many forms of dystonia, a group of disorders characterized by involuntary movements, torsion and tension of several muscles, and an unusual position of the affected body parts.

Signs and symptoms of dystonia 16 vary among affected people and may include muscle contractions that frequently place the affected limb in an abnormal position, which may result in retrocollis, oromandibular dystonia (OMD) and laryngeal dystonia (LD), among others. Dystonia 16 gradually worsens, and finally involvs the muscles of most of the body. In addition, in some cases affected individuals develop mild characteristics of parkinsonism, such as bradykinesia (slow movement), muscle stiffness, tremor and postural instability.

This process is due to mutations in the PRKRA gene (protein activator of interferon induced protein kinase EIF2AK2), located on the long arm of chromosome 2 (2q31.2), which encodes the PACT protein. This protein plays a role in the cell's response to stress, such as exposure to viruses and to harmful molecules called free radicals or other toxic substances. When a cell is under stress, the PACT protein activates the PKR protein, which then deactivates the eIF2α protein. Inactivation of eIF2α reduces protein production, which helps protect cells from damage. PACT activated signals can ultimately lead to cell apoptosis if it remains under stress. In addition, the signals sent by the PACT protein are also important for synaptic plasticity.

At least, eight mutations in the PRKRA gene have been identified in people with dystonia 16, the majority of which consist of amino acid changes in the PACT protein. It is believed that these changes alter the sending of signals sent by the PACT protein in response to stress. Abnormal signaling increases the rate at which cell death occurs. Excessive cell loss in certain regions of the brain is likely to affect the brain's ability to control muscles and movement.

With more frequency, this process is inherited with an autosomal recessive pattern which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease. In some cases, one mutation is inherited from an unaffected parent and the other is a new mutation in the gene that occurs during the formation of reproductive cells in the other parent or at the beginning of embryonic development. Some studies suggest that dystonia 16 can also be inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to express the process.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with the dystonia 16, by means of the complete PCR amplification of the exons of the PRKRA gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).