Database : MEDLINE
Search on : Dystonia and Musculorum and Deformans [Words]
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[PMID]: 26592310
[Au] Autor:Rose AE; Brown RS; Schlieker C
[Ad] Address:a Department of Molecular Biophysics and Biochemistry , Yale University , New Haven , CT , USA and.
[Ti] Title:Torsins: not your typical AAA+ ATPases.
[So] Source:Crit Rev Biochem Mol Biol;50(6):532-49, 2015.
[Is] ISSN:1549-7798
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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. Studying Torsins has significant medical relevance since mutations in Torsins or Torsin-associated proteins result in a variety of congenital human disorders, the most frequent of which is early-onset torsion (DYT1) dystonia, a severe movement disorder. A better understanding of the Torsin system is needed to define the molecular etiology of these diseases, potentially enabling corrective therapy. Here, we provide a comprehensive overview of the Torsin system in metazoans, discuss functional clues obtained from various model systems and organisms and provide a phylogenetic and structural analysis of Torsins and their regulatory cofactors in relation to disease-causative mutations. Moreover, we review recent data that have led to a dramatically improved understanding of these machines at a molecular level, providing a foundation for investigating the molecular defects underlying the associated movement disorders. Lastly, we discuss our ideas on how recent progress may be utilized to inform future studies aimed at determining the cellular role(s) of these atypical molecular machines and their implications for dystonia treatment options.
[Mh] MeSH terms primary: Molecular Chaperones/metabolism
[Mh] MeSH terms secundary: Amino Acid Sequence
Animals
Carrier Proteins/metabolism
Disease Models, Animal
Dystonia Musculorum Deformans/genetics
Dystonia Musculorum Deformans/metabolism
HSC70 Heat-Shock Proteins/metabolism
Humans
Membrane Proteins/metabolism
Molecular Chaperones/analysis
Molecular Chaperones/genetics
Molecular Sequence Data
Mutation
Protein Transport
Sequence Alignment
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; REVIEW
[Nm] Name of substance:0 (Carrier Proteins); 0 (HSC70 Heat-Shock Proteins); 0 (HSPA8 protein, human); 0 (Membrane Proteins); 0 (Molecular Chaperones); 0 (TOR1A protein, human); 0 (TOR1AIP2 protein, human)
[Em] Entry month:1609
[Cu] Class update date: 161104
[Lr] Last revision date:161104
[Js] Journal subset:IM
[Da] Date of entry for processing:151126
[St] Status:MEDLINE
[do] DOI:10.3109/10409238.2015.1091804

  2 / 781 MEDLINE  
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[PMID]: 26419798
[Au] Autor:Sako W; Fujita K; Vo A; Rucker JC; Rizzo JR; Niethammer M; Carbon M; Bressman SB; Ulug AM; Eidelberg D
[Ad] Address:1 Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
[Ti] Title:The visual perception of natural motion: abnormal task-related neural activity in DYT1 dystonia.
[So] Source:Brain;138(Pt 12):3598-609, 2015 Dec.
[Is] ISSN:1460-2156
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of healthy subjects performing this task have revealed selective activation of motor regions during the perception of 'natural' versus 'unnatural' motion (defined respectively as trajectories with kinematic properties that either comply with or violate the two-thirds power law of motion). Several regions with significant connectivity changes in primary dystonia were situated in proximity to normal motion perception pathways, suggesting that abnormalities of these circuits may also be present in this disorder. To determine whether activation responses to natural versus unnatural motion in primary dystonia differ from normal, we used functional magnetic resonance imaging to study 10 DYT1 dystonia and 10 healthy control subjects at rest and during the perception of 'natural' and 'unnatural' motion. Both groups exhibited significant activation changes across perceptual conditions in the cerebellum, pons, and subthalamic nucleus. The two groups differed, however, in their responses to 'natural' versus 'unnatural' motion in these regions. In healthy subjects, regional activation was greater during the perception of natural (versus unnatural) motion (P < 0.05). By contrast, in DYT1 dystonia subjects, activation was relatively greater during the perception of unnatural (versus natural) motion (P < 0.01). To explore the microstructural basis for these functional changes, the regions with significant interaction effects (i.e. those with group differences in activation across perceptual conditions) were used as seeds for tractographic analysis of diffusion tensor imaging scans acquired in the same subjects. Fibre pathways specifically connecting each of the significant functional magnetic resonance imaging clusters to the cerebellum were reconstructed. Of the various reconstructed pathways that were analysed, the ponto-cerebellar projection alone differed between groups, with reduced fibre integrity in dystonia (P < 0.001). In aggregate, the findings suggest that the normal pattern of brain activation in response to motion perception is disrupted in DYT1 dystonia. Thus, it is unlikely that the circuit changes that underlie this disorder are limited to primary sensorimotor pathways.
[Mh] MeSH terms primary: Brain/pathology
Brain/physiopathology
Dystonia Musculorum Deformans/pathology
Dystonia Musculorum Deformans/physiopathology
Motion Perception
[Mh] MeSH terms secundary: Adult
Brain Mapping
Case-Control Studies
Cerebellum/physiopathology
Diffusion Tensor Imaging
Female
Humans
Magnetic Resonance Imaging
Male
Neural Pathways/physiopathology
Pons/physiopathology
Subthalamic Nucleus/physiopathology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Entry month:1605
[Cu] Class update date: 161201
[Lr] Last revision date:161201
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:151124
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awv282

  3 / 781 MEDLINE  
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[PMID]: 26417535
[Au] Autor:Broussolle E; Laurencin C; Bernard E; Thobois S; Danaila T; Krack P
[Ad] Address:Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Lyon, France ; Université Claude Bernard Lyon I, Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Lyon, France ; CNRS UMR 5229, Centre de Neurosciences Cognitives, Bron, France.
[Ti] Title:Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia.
[So] Source:Tremor Other Hyperkinet Mov (N Y);5:332, 2015.
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract: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. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called "simple mannerisms, childish behaviour or fake pathological movements" was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud's pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim's 1911 seminal description of dystonia musculorum deformans in Berlin. DISCUSSION: Brissaud-Meige's misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970-1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society's classification of dystonia.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1509
[Cu] Class update date: 151001
[Lr] Last revision date:151001
[Da] Date of entry for processing:150929
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.7916/D8KD1X74

  4 / 781 MEDLINE  
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[PMID]: 26376866
[Au] Autor:Ruiz M; Perez-Garcia G; Ortiz-Virumbrales M; Méneret A; Morant A; Kottwitz J; Fuchs T; Bonet J; Gonzalez-Alegre P; Hof PR; Ozelius LJ; Ehrlich ME
[Ad] Address:Department of Pediatrics.
[Ti] Title:Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia.
[So] Source:Hum Mol Genet;24(25):7159-70, 2015 Dec 20.
[Is] ISSN:1460-2083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations.
[Mh] MeSH terms primary: Cerebellum/metabolism
DNA-Binding Proteins/metabolism
Dystonia Musculorum Deformans/metabolism
Dystonia Musculorum Deformans/pathology
[Mh] MeSH terms secundary: Animals
DNA-Binding Proteins/genetics
Male
Mice
Mice, Mutant Strains
Mutation
RNA, Messenger/genetics
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (DNA-Binding Proteins); 0 (RNA, Messenger)
[Em] Entry month:1609
[Cu] Class update date: 161220
[Lr] Last revision date:161220
[Js] Journal subset:IM
[Da] Date of entry for processing:151201
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddv384

  5 / 781 MEDLINE  
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[PMID]: 26370418
[Au] Autor:Weisheit CE; Dauer WT
[Ad] Address:Graduate Program in Cellular and Molecular Biology.
[Ti] Title:A novel conditional knock-in approach defines molecular and circuit effects of the DYT1 dystonia mutation.
[So] Source:Hum Mol Genet;24(22):6459-72, 2015 Nov 15.
[Is] ISSN:1460-2083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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. To uniquely address key questions of disease pathogenesis, we generated a conditional Tor1a knock-in allele that is converted from wild-type to DYT1 mutant ('induced' ΔE: Tor1a(i-ΔE)), following Cre recombination. We used this model to perform a gene dosage study exploring the effects of the ΔE mutation at the molecular, neuropathological and organismal levels. These analyses demonstrated that ΔE-torsinA is a hypomorphic allele and showed no evidence for any gain-of-function toxic properties. The unique capabilities of this model also enabled us to test a circuit-level hypothesis of DYT1 dystonia, which predicts that expression of the DYT1 genotype (Tor1a(ΔE/+)) selectively within hindbrain structures will produce an overtly dystonic animal. In contrast to this prediction, we find no effect of this anatomic-specific expression of the DYT1 genotype, a finding that has important implications for the interpretation of the human and mouse diffusion tensor-imaging studies upon which it is based. These studies advance understanding of the molecular effects of the ΔE mutation, challenge current concepts of the circuit dysfunction that characterize the disease and establish a powerful tool that will be valuable for future studies of disease pathophysiology.
[Mh] MeSH terms primary: Dystonia Musculorum Deformans/genetics
Molecular Chaperones/genetics
Mutation
[Mh] MeSH terms secundary: Alleles
Animals
Diffusion Tensor Imaging
Disease Models, Animal
Dystonia Musculorum Deformans/metabolism
Female
Gene Knock-In Techniques
Genotype
Male
Mice
Mice, Transgenic
Molecular Chaperones/metabolism
Neurons/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Dyt1 protein, mouse); 0 (Molecular Chaperones); 0 (TOR1A protein, human)
[Em] Entry month:1609
[Cu] Class update date: 161115
[Lr] Last revision date:161115
[Js] Journal subset:IM
[Da] Date of entry for processing:151023
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddv355

  6 / 781 MEDLINE  
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[PMID]: 26281352
[Au] Autor:Jurek M; Milewski M
[Ti] Title:Funkcja torsyny 1A w patomechanizmie dystonii torsyjnej typu 1. [Torsin 1A and the pathomechanism of torsion dystonia type 1].
[So] Source:Postepy Biochem;61(1):35-41, 2015.
[Is] ISSN:0032-5422
[Cp] Country of publication:Poland
[La] Language:pol
[Ab] Abstract: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.
[Mh] MeSH terms primary: Dystonia Musculorum Deformans/genetics
Dystonia Musculorum Deformans/metabolism
Molecular Chaperones/genetics
Molecular Chaperones/metabolism
[Mh] MeSH terms secundary: Animals
Humans
Mutation
Nuclear Envelope/metabolism
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:0 (Molecular Chaperones); 0 (TOR1A protein, human)
[Em] Entry month:1509
[Cu] Class update date: 150817
[Lr] Last revision date:150817
[Js] Journal subset:IM
[Da] Date of entry for processing:150817
[St] Status:MEDLINE

  7 / 781 MEDLINE  
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[PMID]: 25894231
[Au] Autor:Fox MD; Alterman RL
[Ad] Address:Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.
[Ti] Title:Brain Stimulation for Torsion Dystonia.
[So] Source:JAMA Neurol;72(6):713-9, 2015 Jun.
[Is] ISSN:2168-6157
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract: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. EVIDENCE REVIEW: PubMed was searched for publications on the clinical effect of brain stimulation in dystonia up through December 31, 2014. Recent meta-analyses, consensus statements, and evidence-based guidelines were incorporated. Emphasis was placed on deep brain stimulation (DBS) and randomized clinical trials; however, other stimulation modalities and trial designs were included. For each intervention the mean change in dystonia severity, number of patients studied, and evidence of efficacy based on American Academy of Neurology criteria were determined. FINDINGS: Strong (level B) evidence supports the use of DBS for the treatment of primary generalized or segmental dystonia, especially when due to mutation in the DYT1 gene, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer's cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques, including epidural cortical stimulation and noninvasive brain stimulation, have been investigated, but generally report smaller effect sizes in fewer patients. CONCLUSIONS AND RELEVANCE: Patients with dystonia that is not adequately controlled with standard medical therapy should be referred for consideration of DBS, especially patients with generalized, segmental, or cervical dystonia. Other less-invasive stimulation modalities require further research before being considered a therapeutic alternative.
[Mh] MeSH terms primary: Deep Brain Stimulation/methods
Dystonia Musculorum Deformans/therapy
[Mh] MeSH terms secundary: Humans
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Em] Entry month:1508
[Cu] Class update date: 161019
[Lr] Last revision date:161019
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:150609
[St] Status:MEDLINE
[do] DOI:10.1001/jamaneurol.2015.51

  8 / 781 MEDLINE  
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[PMID]: 25860259
[Au] Autor:Zhang L; McCarthy DM; Sharma N; Bhide PG
[Ad] Address:Department of Biomedical Sciences, Center for Brain Repair, Florida State University College of Medicine, Tallahassee, Florida, United States of America.
[Ti] Title:Dopamine receptor and Gα(olf) expression in DYT1 dystonia mouse models during postnatal development.
[So] Source:PLoS One;10(4):e0123104, 2015.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract: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. METHODOLOGY/PRINCIPAL FINDINGS: We used Dyt1 knock out (Dyt1 KO), Dyt1 ΔGAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT) or human ΔGAG mutant allele (DYT1 hMT). D1R, D2R, and Gα(olf) protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60) male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf) protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice. CONCLUSION/SIGNIFICANCE: We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology.
[Mh] MeSH terms primary: Dystonia Musculorum Deformans/genetics
GTP-Binding Protein alpha Subunits/genetics
Gene Expression
Receptors, Dopamine/genetics
[Mh] MeSH terms secundary: Age Factors
Animals
Animals, Newborn
Brain/metabolism
Disease Models, Animal
Genotype
Humans
Male
Mice
Mice, Transgenic
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (GTP-Binding Protein alpha Subunits); 0 (Receptors, Dopamine)
[Em] Entry month:1512
[Cu] Class update date: 150422
[Lr] Last revision date:150422
[Js] Journal subset:IM
[Da] Date of entry for processing:150411
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0123104

  9 / 781 MEDLINE  
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[PMID]: 25545912
[Au] Autor:Erro R; Hersheson J; Ganos C; Mencacci NE; Stamelou M; Batla A; Thust SC; Bras JM; Guerreiro RJ; Hardy J; Quinn NP; Houlden H; Bhatia KP
[Ad] Address:Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, United Kingdom.
[Ti] Title:H-ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations?
[So] Source:Mov Disord;30(6):828-33, 2015 May.
[Is] ISSN:1531-8257
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract: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. Hence, the question of whether these disorders reflect variable expressivity or pleiotropy of TUBB4A mutations has been raised. We report four unrelated patients with imaging findings either partially or totally consistent with H-ABC syndrome, who were found to have TUBB4A mutations. All four subjects had a relatively homogenous phenotype characterized by severe generalized dystonia with superimposed pyramidal and cerebellar signs, and also bulbar involvement leading to complete aphonia and swallowing difficulties, even though one of the cases had an intermediate phenotype between H-ABC syndrome and DYT4. Genetic analysis of the TUBB4A gene showed one previously described and two novel mutations (c.941C>T; p.Ala314Val and c.900G>T; p.Met300Ile) in the exon 4 of the gene. While expanding the genetic spectrum of H-ABC syndrome, we confirm its radiological heterogeneity and demonstrate that phenotypic overlap with DYT4. Moreover, reappraisal of previously reported cases would also argue against pleiotropy of TUBB4A mutations. We therefore suggest that H-ABC and DYT4 belong to a continuous phenotypic spectrum associated with TUBB4A mutations.
[Mh] MeSH terms primary: Basal Ganglia/pathology
Cerebellum/pathology
Dystonia Musculorum Deformans/genetics
Genetic Pleiotropy
Leukoencephalopathies/genetics
Tubulin/genetics
Voice Disorders/congenital
[Mh] MeSH terms secundary: Adult
Dystonia Musculorum Deformans/pathology
Dystonia Musculorum Deformans/physiopathology
Exons
Female
Heterozygote
Humans
Leukoencephalopathies/pathology
Leukoencephalopathies/physiopathology
Male
Mutation
Phenotype
Voice Disorders/genetics
Voice Disorders/pathology
Voice Disorders/physiopathology
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (TUBB4A protein, human); 0 (Tubulin)
[Em] Entry month:1604
[Cu] Class update date: 170322
[Lr] Last revision date:170322
[Js] Journal subset:IM
[Da] Date of entry for processing:150520
[St] Status:MEDLINE
[do] DOI:10.1002/mds.26129

  10 / 781 MEDLINE  
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[PMID]: 25065529
[Au] Autor:Hallett M
[Ad] Address:Human Motor Control Section, NINDS, Bethesda, MD, USA. hallettm@ninds.nih.gov.
[Ti] Title:The dystonias: a heterogeneous collection.
[So] Source:Eur J Neurol;22(5):741-2, 2015 May.
[Is] ISSN:1468-1331
[Cp] Country of publication:England
[La] Language:eng
[Mh] MeSH terms primary: Blinking/physiology
Cerebellar Diseases/physiopathology
Conditioning (Psychology)/physiology
Dystonia Musculorum Deformans/physiopathology
[Mh] MeSH terms secundary: Female
Humans
Male
[Pt] Publication type:COMMENT; EDITORIAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Em] Entry month:1512
[Cu] Class update date: 150407
[Lr] Last revision date:150407
[Js] Journal subset:IM
[Da] Date of entry for processing:150407
[St] Status:MEDLINE
[do] DOI:10.1111/ene.12526


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