Study Of Two Families Helps Characterize Inherited Movement Disorder

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 LГјbeck,
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."



DYT16, a novel young-onset dystonia-parkinsonism disorder:
identification of a segregating mutation in the stress-response protein
PRKRA

Sarah Camargos, Sonja Scholz, Javier Simon-Sanchez, Coro Paisan-Ruiz,
Patrick Lewis, Dena Hernandez, Jinhui Ding, J Raphael Gibbs, Mark R
Cookson, Jose Bras, Rita Guerreiro, Catarina Resende Oliveira, Andrew
Lees, John Hardy, Francisco Cardoso, Andrew B Singleton

The Lancet Neurology Early Online Publication, 4 Febuary 2008

DOI:10.1016/S1474-4422(08)70022-X

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Here for Abstract



Written by Anna Sophia McKenney