By studying two Brazilian families that each have manifestations of dystonia, researchers have identified a genetic mutation that underlies the condition. The gene coding for PRKRA, a protein in the cellular response to stress and inflammation, contained a mutation (DYT16) in the afflicted patients, according to an Article published early Online in the March edition of The Lancet Neurology.
Dystonia, a presently uncurable neurological disorder that affects movement, is characterized by sustained muscle contractions which often result in repetitive actions, twisting, and abnormal posture. Symptoms often begin in childhood can be extremely painful. Presently, there are 15 genetic mutations that have been identified as associated with hereditary dystonia, named DYT1 through DYT15. Dr Andrew Singleton, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, MD, USA, and Dr Francisco Cardoso, Movement Disorders Clinic of the Federal University of Minas Gerais, Brazil (who led the study), and colleagues, characterized a new dystonia syndrome. This form of the disorder shows an early onset, and is identified by axial muscle involvement, a sardonic smile, laryngeal dystonia and occasionally features similar to Parkinson’s Disease. Unlike patients suffering many other types of dystonia, patients with this form show no response to presently available pharmacological treatments, including levodopa and anticholinergics.
In the study, genomic DNA was isolated from blood samples taken from both patients and family members. These genotypes were compared with the profiles of hundreds of neurologically healthy controls, and patients displaying other movement disorders. By comparing up to 555,000 individual single nucleotide polymorphisms (changes in a single base unit or nucleotide, also known as SNPs) highlighted a relevant mutation in the gene codifying for PRKRA, dubbed DYT16, which follows a recessive mode of inheritance in both of the families.
In conclusion, the authors make a confident statement about the link between this genetic mutation and this manifestation of the disease. “We have described a novel autosomal recessive dystonia- parkinsonism syndrome in Brazilian patients that we have designated DYT16…The absence of the mutation in such a large series of controls and our inability to identify other mutations, despite screening all other genes in the identified region, clearly supports our assertion that mutation in PRKRA is the causative genetic mutation in DYT16.”
A Reflection and Reaction commentary linked to this study, written by Dr Christine Klein, Department of Neurology, University of Lübeck, Germany, she reiterates the need for this type of research: “Mutational analyses of large dystonia patient samples from different ethnic backgrounds are needed to evaluate the frequency of mutations, the phenotypic and mutational spectrum, and, more generally speaking, the
significance of DYT16 dystonia in clinical practice.”
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