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Tremor Other Hyperkinet Mov (N Y) 2018 29;8:568. Epub 2018 May 29.

Laboratory of Experimental and Computational Neuroscience, Department of Biosystems, Federal University of São João del-Rei, São João Del-Rei, Brazil.

In Response To: Giron C, Roze E, Degos, B, Méneret A, Jardel C, Lannuzel A, et al. Adult-onset generalized dystonia as the main manifestation of MEGDEL syndrome. Tremor Other Hyperkinet Mov. Read More

Dev Period Med 2018 ;22(1):33-38

Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.

Objective: Introduction: Torsion dystonia type 1 is the most common form of early-onset primary dystonia. Previous reports have suggested that torsin 1A, a protein mutated in this disease, might function as a chaperone that prevents the toxic aggregation of misfolded polypeptides. The aim of the study: The aim of this study was to verify the chaperone function of torsin 1A by investigating its ability to prevent the aggregation of huntingtin model peptides. Read More

Neuroscience 2018 02 28;371:455-468. Epub 2017 Dec 28.

Raymond G. Perelman Center for Cellular & Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address:

DYT1 dystonia is a neurological disease caused by dominant mutations in the TOR1A gene, encoding for the endoplasmic reticulum (ER)-resident protein torsinA. Recent reports linked expression of the DYT1-causing protein with dysregulation of eIF2α, a key component of the cellular response to ER stress known as the unfolded protein response (UPR). However, the response of the DYT1 mammalian brain to acute ER stress inducers has not been evaluated in vivo. Read More

JBJS Case Connect 2017 Jul-Sep;7(3):e47

1Departments of Orthopaedic Surgery (A.K.B. and M.J.S.) and Neurological Surgery (R.N. and D.M.W.), Allegheny General Hospital, Pittsburgh, Pennsylvania.

Case: An adolescent girl presented with an atypical scoliotic curve, pelvic obliquity, back pain, and lower-extremity paresthesias. A workup revealed generalized primary torsion dystonia. The condition was refractory to medical treatment and necessitated implantation of a deep brain stimulator. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017 Dec;34(6):870-873

Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Email:

Objective: To explore the feasibility of using PCR-based capillary electrophoresis method to analysis mutation of the TOR1A gene in a family affected with primary torsion dystonia (PTD).

Methods: Peripheral blood sample was collected from proband and amnionic fluid from her fetus for the extraction of DNA. The 5th exon of the TOR1A gene and its flanking sequences were amplified with PCR and analyzed with agarose electrophoresis, fluorescence labeled fragment analysis and Sanger sequencing. Read More

Biochem Biophys Res Commun 2018 01 7;495(1):346-352. Epub 2017 Nov 7.

Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan. Electronic address:

Dystonia-1 (DYT1) is an autosomal dominant early-onset torsion form of dystonia, a neurological disease affecting movement. DYT1 is the prototypic hereditary dystonia and is caused by the mutation of the tor1a gene. The gene product has chaperone functions important for the control of protein folding and stability. Read More

Arch Clin Neuropsychol 2017 Nov;32(7):888-905

Cognitive Motor Neuroscience Group, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London WC1N 3BG, UK.

Dystonia is a hyperkinetic movement disorder, characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Executive dysfunction is a feature of cognitive function in idiopathic and DYT1 dystonia. Psychiatric morbidity is increased in dystonia, and depression, anxiety, obsessive compulsive disorders are the most common disorders. Read More

Mov Disord 2017 Nov 26;32(11):1537-1545. Epub 2017 Aug 26.

Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.

Dystonia is a common movement disorder that devastates the lives of many patients, but the etiology of this disorder remains poorly understood. Dystonia has traditionally been considered a disorder of the basal ganglia. However, growing evidence suggests that the cerebellum may be involved in certain types of dystonia, raising several questions. Read More

Dis Model Mech 2017 09 2;10(9):1129-1140. Epub 2017 Aug 2.

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 5117 Centre Avenue, UPCI Research Pavilion, 2.42e, Pittsburgh, PA 15213, USA.

Dystonia is the third most common movement disorder, but its diagnosis and treatment remain challenging. One of the most severe types of dystonia is early-onset torsion dystonia (EOTD). The best studied and validated EOTD-associated mutation, torsinAΔE, is a deletion of a C-terminal glutamate residue in the AAA+ ATPase torsinA. Read More

Neurobiol Dis 2017 Oct 1;106:124-132. Epub 2017 Jul 1.

Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA; Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA. Electronic address:

Multiple lines of evidence implicate striatal dysfunction in the pathogenesis of dystonia, including in DYT1, a common inherited form of the disease. The impact of striatal dysfunction on connected motor circuits and their interaction with other brain regions is poorly understood. Conditional knock-out (cKO) of the DYT1 protein torsinA from forebrain cholinergic and GABAergic neurons creates a symptomatic model that recapitulates many characteristics of DYT1 dystonia, including the developmental onset of overt twisting movements that are responsive to antimuscarinic drugs. Read More

Mov Disord 2017 Oct 19;32(10):1348-1355. Epub 2017 Jun 19.

Cognitive Motor Neuroscience Group, Sobell Department of Motor Neuroscience & Movement Disorders, University College London (UCL) Institute of Neurology, The National Hospital for Neurology & Neurosurgery, London, UK.

Dystonia is a common movement disorder. In this paper, we review the literature on cognitive function in idiopathic and DYT1 dystonia. In idiopathic or DYT1 dystonia, cognition is largely intact with only isolated executive dysfunction. Read More

Elife 2017 02 15;6. Epub 2017 Feb 15.

Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States.

DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA. How these mutations cause dystonia remains unknown. Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients, possibly due to differential developmental compensation between rodents and humans. Read More

Neuron 2016 Dec 8;92(6):1238-1251. Epub 2016 Dec 8.

Department of Neurology, Duke University, Durham, NC 27708, USA; Department of Neurobiology, Duke University, Durham, NC 27708, USA. Electronic address:

Dystonia is a brain disorder causing involuntary, often painful movements. Apart from a role for dopamine deficiency in some forms, the cellular mechanisms underlying most dystonias are currently unknown. Here, we discover a role for deficient eIF2α signaling in DYT1 dystonia, a rare inherited generalized form, through a genome-wide RNAi screen. Read More

Mov Disord 2017 03 2;32(3):371-381. Epub 2016 Dec 2.

Vlaams Instituut voor Biotechnologie Centre for the Biology of Disease, Leuven, Belgium.

Heterozygosity for a 3-base pair deletion (ΔGAG) in TOR1A/torsinA is one of the most common causes of hereditary dystonia. In this review, we highlight current understanding of how this mutation causes disease from research spanning structural biochemistry, cell science, neurobiology, and several model organisms. We now know that homozygosity for ΔGAG has the same effects as Tor1a , implicating a partial loss of function mechanism in the ΔGAG/+ disease state. Read More

Behav Brain Res 2017 01 18;317:536-541. Epub 2016 Oct 18.

Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103, Leipzig, Germany. Electronic address:

Hereditary generalized dystonia is often caused by a GAG deletion in TOR1A (DYT1) that encodes for the protein torsinA. Although mutation carriers show alterations in neuronal connectivity and sensorimotor deficits, only 30% develop dystonia. Uncovering the factors triggering the dystonic symptoms and underlying pathophysiology would greatly benefit the development of more effective therapies. Read More

Acta Neuropathol Commun 2016 08 17;4(1):85. Epub 2016 Aug 17.

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Mov Disord 2016 11 25;31(11):1739-1743. Epub 2016 Jul 25.

Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Background: DYT1 mutation is characterized by focal to generalized dystonia and incomplete penetrance. To explore the complex perturbations in the different neural networks and the mutual interactions among them, we studied symptomatic and asymptomatic DTY1 mutation carriers by resting-state functional MRI.

Methods: A total of 7 symptomatic DYT1, 10 asymptomatic DYT1, and 26 healthy controls were considered. Read More

BMJ Case Rep 2016 Jul 22;2016. Epub 2016 Jul 22.

Unit of Neurology, IRCCS San Martino University Hospital, Genoa, Italy.

Primary torsion dystonia is a movement disorder characterised by sustained or intermittent involuntary muscle contractions causing abnormal movements, postures or both. In this study, 3 brothers affected by inherited primary dystonia 16 (DYT16) began an oral therapy with high-dose thiamine from November to December 2015. After 3 months, an important improvement of the motor symptoms was observed. Read More

Exp Ther Med 2016 Aug 25;12(2):661-666. Epub 2016 May 25.

Institute of Neurosurgery, The PLA Navy General Hospital, Beijing 100048, P.R. China.

Primary torsion dystonia (PTD) occurs due to a genetic mutation and often advances gradually. Currently, there is no therapy available that is able to inhibit progression. Neural stem cells (NSCs) are being investigated as potential therapies for neurodegenerative diseases, such as stroke and trauma. Read More

Plant Cell 2016 05 25;28(5):997-8. Epub 2016 Apr 25.

Science Editor

Plant Cell 2016 05 25;28(5):1078-93. Epub 2016 Apr 25.

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering and Institute of Biodiversity Sciences, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, China

Transcriptional regulation is one of the most important mechanisms controlling development and cellular functions in plants and animals. The Arabidopsis thaliana bHLH transcription factor (TF) DYSFUNCTIONL TAPETUM1 (DYT1) is required for normal male fertility and anther development and activates the expression of the bHLH010/bHLH089/bHLH091 genes. Here, we showed that DYT1 is localized to both the cytoplasm and nucleus at anther stage 5 but specifically to the nucleus at anther stage 6 and onward. Read More

Mol Neurobiol 2017 03 20;54(2):939-942. Epub 2016 Jan 20.

Laboratory of Medical Genetics and Molecular Pathology, Faculty of Medicine and Pharmacy Hassan II University of Casablanca, Casablanca, Morocco.

Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder with onset in the first two decades of life. Mutations in the epsilon-sarcoglycan gene (SGCE, DYT11) on chromosome 7q21-q31 represent the major genetic cause of M-D in some populations. The syndrome was related with mutations in two other genes (DRD2 and DYT1). Read More

Crit Rev Biochem Mol Biol 2015 13;50(6):532-49. Epub 2015 Oct 13.

a Department of Molecular Biophysics and Biochemistry , Yale University , New Haven , CT , USA and.

Torsin ATPases (Torsins) belong to the widespread AAA+ (ATPases associated with a variety of cellular activities) family of ATPases, which share structural similarity but have diverse cellular functions. Torsins are outliers in this family because they lack many characteristics of typical AAA+ proteins, and they are the only members of the AAA+ family located in the endoplasmic reticulum and contiguous perinuclear space. While it is clear that Torsins have essential roles in many, if not all metazoans, their precise cellular functions remain elusive. Read More

Brain 2015 Dec 29;138(Pt 12):3598-609. Epub 2015 Sep 29.

1 Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA

Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. Read More

Tremor Other Hyperkinet Mov (N Y) 2015 21;5:332. Epub 2015 Sep 21.

Département de Psychiatrie et de Neurologie, Unité des Mouvements Anormaux, Centre Hospitalier Universitaire de Grenoble, Grenoble, France ; INSERM Unité 836, Grenoble Institut des Neurosciences, Grenoble, France ; Université Joseph Fourier, Grenoble, France.

Background: Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste.

Results: In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. Read More

Hum Mol Genet 2015 Dec 16;24(25):7159-70. Epub 2015 Sep 16.

Department of Pediatrics, Department of Genetics and Genomic Sciences, Department of Neurology,

DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. Read More

Hum Mol Genet 2015 Nov 14;24(22):6459-72. Epub 2015 Sep 14.

Department of Neurology and Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

DYT1 dystonia, the most common inherited form of primary dystonia, is a neurodevelopmental disease caused by a dominant mutation in TOR1A. This mutation ('ΔE') removes a single glutamic acid from the encoded protein, torsinA. The effects of this mutation, at the molecular and circuit levels, and the reasons for its neurodevelopmental onset, remain incompletely understood. Read More

Postepy Biochem 2015 ;61(1):35-41

Torsin 1A is a protein mutated in torsion dystonia type 1, a hereditary neurological disorder of early onset and variable clinical picture. The basic cellular function of torsin 1A, a polypeptide localized predominantly in the endoplasmic reticulum and nuclear envelope, remains unknown, although the protein is suspected of being involved in many different cellular processes, including regulating a proper structure and function of nuclear envelope, contributing to the synaptic vesicular trafficking, or assisting in proper folding of misfolded proteins. This review summarizes the current state of knowledge regarding the potential functions of torsin 1A in the context of hypothetical pathomechanisms responsible for torsion dystonia type 1. Read More

Sleep Med Rev 2016 Apr 9;26:95-107. Epub 2015 May 9.

Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.

Patients with primary dystonia, the third most prevalent movement disorder, suffer from a markedly reduced quality of life. This might, at least in part, be mediated by non-motor symptoms, including sleep disturbances. Characterising and treating sleep disturbances might provide new inroads to improve relevant patient-centred outcomes. Read More

JAMA Neurol 2015 Jun;72(6):713-9

Division of Neurosurgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Importance: Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly used.

Objectives: To review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation and to discuss recent advances relevant to patient selection, surgical approach, programming, and mechanism of action. Read More

PLoS One 2015 10;10(4):e0123104. Epub 2015 Apr 10.

Department of Biomedical Sciences, Center for Brain Repair, Florida State University College of Medicine, Tallahassee, Florida, United States of America.

Background: DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated. Read More

Mov Disord 2015 May 27;30(6):828-33. Epub 2014 Dec 27.

Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, United Kingdom.

Recently, mutations in the TUBB4A gene have been found to underlie hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) syndrome, a rare neurodegenerative disorder of infancy and childhood. TUBB4A mutations also have been described as causative of DYT4 ("hereditary whispering dysphonia"). However, in DYT4, brain imaging has been reported to be normal and, therefore, H-ABC syndrome and DYT4 have been construed to be different disorders, despite some phenotypic overlap. Read More

PLoS One 2014 2;9(12):e113732. Epub 2014 Dec 2.

Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, SACS, Universidade de Aveiro, Aveiro, Portugal.

Lamina associated polypeptide 1 (LAP1) is an integral protein of the inner nuclear membrane that is ubiquitously expressed. LAP1 binds to lamins and chromatin, probably contributing to the maintenance of the nuclear envelope architecture. Moreover, LAP1 also interacts with torsinA and emerin, proteins involved in DYT1 dystonia and X-linked Emery-Dreifuss muscular dystrophy disorder, respectively. Read More

PLoS One 2014 7;9(11):e110086. Epub 2014 Nov 7.

Neuroscience Center, Department of Neurology, and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA, United States of America.

Dystonia is a neurological disorder in which sustained muscle contractions induce twisting and repetitive movements or abnormal posturing. DYT1 early-onset primary dystonia is the most common form of hereditary dystonia and is caused by deletion of a glutamic acid residue (302/303) near the carboxyl-terminus of encoded torsinA. TorsinA is localized primarily within the contiguous lumen of the endoplasmic reticulum (ER) and nuclear envelope (NE), and is hypothesized to function as a molecular chaperone and an important regulator of the ER stress-signaling pathway, but how the mutation in torsinA causes disease remains unclear. Read More

Semin Neurol 2014 Jul 5;34(3):306-11. Epub 2014 Sep 5.

Segawa Neurological Clinic for Children, Tokyo, Japan.

DYT1 and DYT5 are early-onset dominant inherited dystonias. DYT1 is caused by mutations of the TOR1A gene, located on 9q34, which causes dysfunction of the D1 direct pathway or the indirect pathway. Dysfunction of the former causes postural-type and segmental dystonia; the latter causes action-type dystonia. Read More

Eur J Neurol 2015 May 26;22(5):741-2. Epub 2014 Jul 26.

Human Motor Control Section, NINDS, Bethesda, MD, USA.

Eur J Neurol 2015 May 18;22(5):762-7. Epub 2014 Jul 18.

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.

Background And Purpose: Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Read More

J Neurol Neurosurg Psychiatry 2015 Mar 24;86(3):331-5. Epub 2014 Jun 24.

Dept of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Belfield, Dublin, Ireland.

Background: Adult onset primary torsion dystonia (AOPTD) is a poorly penetrant autosomal dominant disorder; most gene carriers are non-manifesting despite having reached an adequate age for penetrance. It is hypothesised that genetic, epigenetic and environmental factors may exert protective or deleterious effects on penetrance of AOPTD. By examining environmental exposure history in cervical dystonia patients and their similarly aged unaffected siblings we aimed to determine the role of previous environmental exposures in relation to disease penetrance. Read More

J Clin Invest 2014 Jul 17;124(7):3080-92. Epub 2014 Jun 17.

Lack of a preclinical model of primary dystonia that exhibits dystonic-like twisting movements has stymied identification of the cellular and molecular underpinnings of the disease. The classical familial form of primary dystonia is caused by the DYT1 (ΔE) mutation in TOR1A, which encodes torsinA, AAA⁺ ATPase resident in the lumen of the endoplasmic reticular/nuclear envelope. Here, we found that conditional deletion of Tor1a in the CNS (nestin-Cre Tor1a(flox/-)) or isolated CNS expression of DYT1 mutant torsinA (nestin-Cre Tor1a(flox/ΔE)) causes striking abnormal twisting movements. Read More

J Clin Invest 2014 Jul 17;124(7):2848-50. Epub 2014 Jun 17.

A common form of the hyperkinetic movement disorder dystonia is caused by mutations in the gene TOR1A (located within the DYT1 locus), which encodes the ATPase torsinA. The underlying neurobiological mechanisms that result in dystonia are poorly understood, and progress in the field has been hampered by the absence of a dystonia-like phenotype in animal models with genetic modification of Tor1a. In this issue of the JCI, Liang et al. Read More

Hum Mutat 2014 Sep 17;35(9):1114-22. Epub 2014 Jul 17.

Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

A three-nucleotide (GAG) deletion (ΔE) in TorsinA (TOR1A) has been identified as the most common cause of dominantly inherited early-onset torsion dystonia (DYT1). TOR1A encodes a chaperone-like AAA+-protein localized in the endoplasmic reticulum. Currently, only three additional, likely mutations have been reported in single dystonia patients. Read More

Hum Mutat 2014 Sep 17;35(9):1101-13. Epub 2014 Jul 17.

Molecular Neurogenetics Unit, Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts; Department of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany.

Early-onset dystonia is associated with the deletion of one of a pair of glutamic acid residues (c.904_906delGAG/c.907_909delGAG; p. Read More

J Neurosci Methods 2014 Jul 29;232:181-188. Epub 2014 May 29.

Department of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, GERMANY.

Background: Microfluidic platforms for quantitative evaluation of cell biologic processes allow low cost and time efficient research studies of biological and pathological events, such as monitoring cell migration by real-time imaging. In healthy and disease states, cell migration is crucial in development and wound healing, as well as to maintain the body's homeostasis.

New Method: The microfluidic chambers allow precise measurements to investigate whether fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary neurologic disease--DYT1 dystonia, have decreased migration properties when compared to control cells. Read More

Parkinsonism Relat Disord 2014 Jul 13;20(7):782-5. Epub 2014 Apr 13.

Department of Neurology, University of Groningen, The Netherlands. Electronic address:

The dystonias are a clinical heterogeneous group with a complex genetic background. To gain more insight in genetic risk factors in dystonia we used a pathway sequence approach in patients with an extreme dystonia phenotype (n = 26). We assessed all coding and non-coding variants in candidate genes in D1-like subclass of dopamine receptor genes (DRD1, DRD5) and the synaptic vesicle pathway linked to torsinA (TOR1A, STON2, SNAPIN, KLC1 and THAP1), spanning 96 Kb. Read More

Zh Nevrol Psikhiatr Im S S Korsakova 2014 ;114(2):21-7

Forty-three patients with primary dystonia underwent neuropsychological assessment according to the method of A.R. Luria. Read More

J Biol Chem 2014 May 13;289(18):12727-47. Epub 2014 Mar 13.

From the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.

Early-onset torsion dystonia (EOTD) is a neurological disorder characterized by involuntary and sustained muscle contractions that can lead to paralysis and abnormal posture. EOTD is associated with the deletion of a glutamate (ΔE) in torsinA, an endoplasmic reticulum (ER) resident AAA(+) ATPase. To date, the effect of ΔE on torsinA and the reason that this mutation results in EOTD are unclear. Read More

JAMA Neurol 2014 Apr;71(4):490-4

Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.

Importance: Mutations in the GNAL gene have recently been shown to cause primary torsion dystonia. The GNAL-encoded protein (Gαolf) is important for dopamine D1 receptor function and odorant signal transduction. We sequenced all 12 exons of GNAL in 461 patients from Germany, Serbia, and Japan, including 318 patients with dystonia (190 with cervical dystonia), 51 with hyposmia and Parkinson disease, and 92 with tardive dyskinesia or acute dystonic reactions. Read More

Hum Mol Genet 2014 May 30;23(10):2694-710. Epub 2013 Dec 30.

Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6.

A newly identified lethal form of hereditary sensory and autonomic neuropathy (HSAN), designated HSAN-VI, is caused by a homozygous mutation in the bullous pemphigoid antigen 1 (BPAG1)/dystonin gene (DST). The HSAN-VI mutation impacts all major neuronal BPAG1/dystonin protein isoforms: dystonin-a1, -a2 and -a3. Homozygous mutations in the murine Dst gene cause a severe sensory neuropathy termed dystonia musculorum (dt). Read More

PLoS One 2013 19;8(11):e80793. Epub 2013 Nov 19.

Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.

DYT1 dystonia is the most common hereditary form of primary torsion dystonia. This autosomal-dominant disorder is characterized by involuntary muscle contractions that cause sustained twisting and repetitive movements. It is caused by an in-frame deletion in the TOR1A gene, leading to the deletion of a glutamic acid residue in the torsinA protein. Read More

Mov Disord 2014 Jan 22;29(1):143-7. Epub 2013 Oct 22.

Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.

Background: Rare autosomal-dominant mutations in ANO3 and GNAL have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement.

Methods: We used high-resolution melting to screen all exons of ANO3 and GNAL for rare sequence variants in a population of 342 German individuals with mainly sporadic PTD and 376 general population controls.

Results: We identified 2 novel missense variants in ANO3 (p. Read More