Search Our Scientific Publications & Authors

Zhonghua Er Ke Za Zhi 2020 Feb;58(2):123-128

Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants. The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children's Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. Read More

PLoS One 2019 5;14(12):e0226080. Epub 2019 Dec 5.

Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.

In early-onset generalized torsion dystonia, caused by a GAG deletion in TOR1A (DYT1), enhanced striatal cholinergic activity has been suggested to be critically involved. Previous studies have shown increased acetylcholine levels in the striatum of DYT1 knock-in (KI) mice. Ex vivo data indicated that muscarinic receptor antagonists normalize the activity of striatal cholinergic interneurons. Read More

Prog Brain Res 2019 21;249:251-260. Epub 2019 Jun 21.

Motor Control and Movement Disorder Group, Institute of Molecular and Clinical Sciences, St George's University of London, London, United Kingdom.

Clinical movement disorders are classified by an algorithm implemented by a practising movement disorder specialist based on information extracted during the history and clinical examination of a patient. Most simply, dystonia, is a classifier which is reached when a predominant abnormality of posture is noted. In this chapter we summarize studies that have used a variety of techniques to probe beyond the clinical examination and study kinematic features experimentally. Read More

Neurobiol Dis 2019 05 30;125:115-122. Epub 2019 Jan 30.

Department of Pharmacology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA. Electronic address:

Trihexyphenidyl, a nonselective muscarinic receptor antagonist, is the small molecule drug of choice for the treatment of DYT1 dystonia, but it is poorly tolerated due to significant side effects. A better understanding of the mechanism of action of trihexyphenidyl is needed for the development of improved treatments. Because DTY1 dystonia is associated with both abnormal cholinergic neurotransmission and abnormal dopamine regulation, we tested the hypothesis that trihexyphenidyl normalizes striatal dopamine release in a mouse model of DYT1 dystonia using ex vivo fast scan cyclic voltammetry and in vivo microdialysis. Read More

AJNR Am J Neuroradiol 2019 01;40(1):178-183

Hospital of the Institute of Neurology (X.-E.Y., R.-M.Y., Y.-Z.H.), Anhui University of Chinese Medicine, Hefei, China.

Background And Purpose: Neurologic Wilson disease is an inherited disease characterized by a copper metabolic disorder that causes damage to many organs, especially the brain. Few studies report the relationships between these neurologic symptoms and MR imaging of the brain. Therefore, we investigated the correlation of brain abnormalities in patients with neurologic Wilson disease with their clinical symptoms, age of onset, and lag time to diagnosis. Read More

Hum Mol Genet 2019 04;28(8):1343-1356

Davee Department of Neurology.

Dystonia is a movement disorder characterized by involuntary and repetitive co-contractions of agonist and antagonist muscles. Dystonia 6 (DYT6) is an autosomal dominant dystonia caused by loss-of-function mutations in the zinc finger transcription factor THAP1. We have generated Thap1 knock-out mice with a view to understanding its transcriptional role. Read More

EMBO Mol Med 2019 01;11(1)

Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy

Dopamine D2 receptor signaling is central for striatal function and movement, while abnormal activity is associated with neurological disorders including the severe early-onset dystonia. Nevertheless, the mechanisms that regulate D2 receptor signaling in health and disease remain poorly understood. Here, we identify a reduced D2 receptor binding, paralleled by an abrupt reduction in receptor protein level, in the striatum of juvenile mice. Read More

JAMA Neurol 2019 02;76(2):211-216

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

Importance: Anecdotal evidence suggests that deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in ameliorating dystonia in X-linked dystonia parkinsonism (XDP), a disease that is usually refractive to medical therapy.

Objective: To determine the efficacy of GPi-DBS in a cohort of patients with XDP in a prospective study and identify predictors of postoperative outcomes.

Design, Setting, And Participants: This observational prospective cohort study enrolled patients in February 2013 and was completed in December 2014. Read More

Brain Res 2019 03 23;1706:24-31. Epub 2018 Oct 23.

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 a dominant mutation that results in the loss of a glutamic acid in the endoplasmic reticulum-resident protein torsinA. Currently, treatments are symptomatic and only provide partial relief. Multiple reports support the hypothesis that selectively reducing expression of mutant torsinA without affecting levels of the wild type protein should be beneficial. Read More

Parkinsonism Relat Disord 2019 01 31;58:63-69. Epub 2018 Aug 31.

Movement Disorders Program, Atlantic Neuroscience Institute, Overlook Medical Center, AHS, Summit, NJ, USA; The Center for Neurological and Neurodevelopmental Health, NJ, USA. Electronic address:

Objective: To individuate morphometric changes and prevalent types of intraneuronal inclusions in nigral neurons of DYT1 dystonia autopsy-brains.

Methods: Using precise methods of quantification, such as unbiased stereology, we measured cellular and subcellular volumes of neuromelanin-containing (pigmented) neurons in the substantia nigra (SN) of DYT1 carriers with and without manifestation of generalized dystonia (manif-DYT1 and non-manif-DYT1, respectively), non-DYT1 carriers manifesting generalized dystonia (manif-non-DYT1) patients, and age-matched control subjects (controls). A total of four DYT1 carriers (two manif-DYT1 and two non-manif-DYT1), six manif-non-DYT1 carriers, and six controls autopsy-brains were available for these neuropathological-morphometric analyses. Read More

Brain 2018 10;141(10):2995-3008

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

X-linked dystonia-parkinsonism is a neurodegenerative movement disorder characterized by adult-onset dystonia combined with parkinsonism over the disease course. Previous imaging and pathological findings indicate exclusive striatal atrophy with predominant pathology of the striosomal compartment in the dystonic phase of X-linked dystonia-parkinsonism. The striosome occupies 10-15% of the entire striatal volume and the density of striosomes follows a rostrocaudal gradient with the rostral striatum being considered striosome-rich. Read More

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

Sci Rep 2018 02 26;8(1):3653. Epub 2018 Feb 26.

Galea Lab, School of Psychology, University of Birmingham, Birmingham, B15 2TT, UK.

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. 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

Plant Cell 2017 08 26;29(8):1800-1802. Epub 2017 Jul 26.

Center for Applied Plant Sciences andDepartment of Molecular Genetics,The Ohio State University,Columbus, Ohio 43210

Plant Cell 2017 08 26;29(8):1803-1805. Epub 2017 Jul 26.

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, 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 200433, China

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

Oper Neurosurg (Hagerstown) 2018 05;14(5):597

Department of Neurosurgery, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, Pennsylvania.

Background And Importance: Primary generalized dystonia (PGD) is a genetic form of dystonia that frequently displays pharmacological resistance and progresses quickly after onset. Deep brain stimulation (DBS) has been used successfully to treat refractory dystonia, specifically globus pallidus interna (GPi) DBS for DYT1-positive PGD patients. Long-term follow-up of the safety and efficacy falls short of the longevity seen in other diseases treated with DBS. 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

Mov Disord 2016 11 31;31(11):1633-1639. Epub 2016 May 31.

Department of Neurology, College of Medicine,, College of Medicine, University of Florida, Gainesville, Florida, USA.

Introduction: DYT1 dystonia is an autosomal-dominant movement disorder characterized by abnormal, often repetitive, movements and postures. Its hallmark feature is sustained or intermittent contractions of muscles involving co-contractions of antagonist muscle pairs. The symptoms are relieved with the anticholinergic drug trihexyphenidyl. 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