Researchers have reported a new inherited dystonia syndrome, a movement disorder, in two Brazilian families, and have identified the genetic mutation underlying the condition. The patients carry a mutation (DYT16) in the gene that codifies for PRKRA, a protein involved in the cellular response to stress and inflammation. These are conclusions of an Article published early online in the March edition of The Lancet Neurology.
Dystonia is “a neurological disorder that causes involuntary, sustained muscle contractions that result in repetitive movements, twisting and abnormal postures.�* It is an incurable condition with symptoms that can be very painful and often start in childhood. To date, 15 genetic mutations have been associated with hereditary dystonia (DYT1 through to 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 Mias Gerais, Brazil (who led the study), and colleagues, describe a new early-onset dystonia syndrome, characterized by “axial muscle involvement, sardonic smile, laryngeal dystonia and, in some cases, parkinsonian features.� Unlike patients with some other forms of dystonia, these patients do not respond to any available pharmacological treatment for dystonia, including levodopa and anticholinergics.
The researchers obtained genomic DNA from blood samples of patients and family members. They compared their genotypes with those from hundreds of neurologically healthy controls and patients with other movement disorders. The genome wide analysis of more than 555000 individual SNPs (single nucleotide polymorphisms – or a single change of the base units which make up DNA) showed that the patients carry a mutation in the gene codifying for PRKRA, which they have named DYT16. The disease follows a recessive mode of inheritance in both families.
The authors conclude: “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�.
In a linked commentary, Dr Christine Klein, Department of Neurology, University of Lübeck, Germany, says: “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.
*Notes to editors: see http://www.mayoclinic.com/health/dystonia/DS00684 for this definition
For Dr Andrew Singleton, Laboratory of Neurogenetics, National Insititute on Aging, National Institutes of Health, MD, USA, please contact Margaret Vaughn T) +1 301-496-1752 E) vaughnms@mail.nih.gov
Dr Christine Klein, Department of Neurology, University of Lübeck, Germany contact by e-mail only E) christine.klein@neuro.uni-luebeck.de
Journal
The Lancet Neurology