MJD
MCID: MCH002
MIFTS: 62

Machado-Joseph Disease (MJD)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Machado-Joseph Disease

MalaCards integrated aliases for Machado-Joseph Disease:

Name: Machado-Joseph Disease 57 12 25 20 43 53 58 73 36 13 54 44 15 71
Sca3 57 12 25 20 43 58 73
Mjd 57 12 20 43 58 73
Spinocerebellar Ataxia Type 3 12 25 43 58
Spinocerebellar Ataxia 3 57 12 20 73
Azorean Disease 12 43 29 6
Nigrospinodentatal Degeneration 57 20 73
Azorean Neurologic Disease 57 20 73
Spinopontine Atrophy 57 20 71
Nigro-Spino-Dentatal Degeneration with Nuclear Ophthalmoplegia 58
Azorean Disease of the Nervous System 58
Spinocerebellar Ataxia 3; Sca3 57
Spinocerebellar Atrophy Type 3 20
Spinocerebellar Atrophy Iii 57
Spinocerebellar Atrophy 73
Disease, Machado-Joseph 39
Ataxia, Spinocerebellar 71
Machado Disease 58
Azorean Ataxia 43

Characteristics:

Orphanet epidemiological data:

58
spinocerebellar ataxia type 3
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide),1-9/100000 (Portugal),1-9/100000 (Japan); Age of onset: Adolescent,Adult,Childhood; Age of death: adult;

OMIM®:

57 (Updated 05-Mar-2021)
Miscellaneous:
genetic anticipation
progressive disorder
onset in third to fourth decade
wide clinical variability
normal alleles contain up to 44 repeats
pathogenic alleles contain 52 to 86 repeats
incomplete penetrance with 45 to 51 repeats

Inheritance:
autosomal dominant


HPO:

31
machado-joseph disease:
Inheritance autosomal dominant inheritance genetic anticipation
Onset and clinical course progressive


GeneReviews:

25
Penetrance In sca3, penetrance approaches 100% and is age related....

Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Machado-Joseph Disease

MedlinePlus Genetics : 43 Spinocerebellar ataxia type 3 (SCA3) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA3 include speech difficulties, uncontrolled muscle tensing (dystonia), muscle stiffness (spasticity), rigidity, tremors, bulging eyes, and double vision. People with this condition may experience sleep disorders such as restless leg syndrome or REM sleep behavior disorder. Restless leg syndrome is a condition characterized by numbness or tingling in the legs accompanied by an urge to move the legs to stop the sensations. REM sleep behavior disorder is a condition in which the muscles are active during the dream (REM) stage of sleep, so an affected person often acts out his or her dreams. These sleep disorders tend to leave affected individuals feeling tired during the day.Over time, individuals with SCA3 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches (fasciculations), and swallowing difficulties. Individuals with SCA3 may have problems with memory, planning, and problem solving.Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear.

MalaCards based summary : Machado-Joseph Disease, also known as sca3, is related to olivopontocerebellar atrophy and spinocerebellar degeneration, and has symptoms including ataxia, abnormality of extrapyramidal motor function and bradykinesia. An important gene associated with Machado-Joseph Disease is ATXN3 (Ataxin 3), and among its related pathways/superpathways are Spinocerebellar ataxia and Protein processing in endoplasmic reticulum. The drugs Lithium carbonate and Glutamic acid have been mentioned in the context of this disorder. Affiliated tissues include eye, tongue and cerebellum, and related phenotypes are hyperreflexia and abnormal pyramidal sign

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by slow degeneration of the hindbrain and has material basis in expansion of CAG triplet repeats (glutamine) in the ATXN3 gene.

GARD : 20 Spinocerebellar ataxia 3 (SCA3) is a rare, inherited form of ataxia. Signs and symptoms may begin between childhood and late adulthood and vary greatly. Symptoms may include slowly progressive clumsiness in the arms and legs; a manner of walking (gait) that may be mistaken for drunkenness; difficulty speaking and swallowing; impaired eye movements or vision; and lower limb spasticity. Some people with SCA3 develop dystonia or symptoms similar to those of Parkinson's disease; twitching of the face or tongue; nerve damage (neuropathy); or problems with urination and the autonomic nervous system. SCA3 is caused by a mutation in the ATXN3 gene and inheritance is autosomal dominant. There is no medication that slows the progressive course of the disease; management aims to relieve some symptoms and improve quality of life. Life expectancy ranges from the mid-30s for those with the most severe forms, to a nearly normal life expectancy for those with milder forms.

OMIM® : 57 Machado-Joseph disease, named for affected families of Azorean extraction, is an autosomal dominant progressive neurologic disorder characterized principally by ataxia, spasticity, and ocular movement abnormalities. Although independently described as a seemingly separate disorder, spinocerebellar ataxia-3 is now known to be the same as Machado-Joseph disease. Three classic clinical subtypes of MJD are recognized: type 1 with early onset and marked pyramidal and dystonic signs; type 2, or pure, with predominant cerebellar ataxia; and type 3 with later-onset and peripheral neuropathy (Franca et al., 2008). (109150) (Updated 05-Mar-2021)

NINDS : 53 Machado-Joseph disease (MJD), which is also called spinocerebellar ataxia type 3, is a rare hereditary ataxia (ataxia is a medical term meaning lack of muscle control). The disease is characterized by slowly progressive clumsiness and weakness in the arms and legs, spasticity, a staggering lurching gait easily mistaken for drunkenness, difficulty with speech and swallowing, involuntary eye movements, double vision, and frequent urination. Some individuals also have dystonia (sustained muscle contractions that cause twisting of the body and limbs, repetitive movements, abnormal postures, and rigidity) or symptoms similar to those of Parkinson's disease. Others have twitching of the face or tongue, or peculiar bulging eyes.  Almost all individuals with MJD experience vision problems, including double vision or blurred vision, loss of the ability to distinguish color and/or contrast, and inability to control eye movements.

KEGG : 36 Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is one of the most common hereditary ataxias and is distributed worldwide. MJD is an autosomal dominant neurodegenerative disorder, involving predominantly the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Minor, but more specific, features such as external progressive ophthalmoplegia (EPO), dystonia, intention fasciculation-like movements of facial and lingual muscles, as well as bulging eyes, may also be of major importance for the clinical diagnosis of MJD. The mean age at onset is around 40 years. MJD is associated with CAG repeat expansions in the ATXN3 gene. CAG repeat varies in size among affected persons. There is no effective treatment of ataxia. Case series and small controlled trials of several medications including antianxiolytics, antidepressants, and antiepileptics have shown limited efficacy.

UniProtKB/Swiss-Prot : 73 Spinocerebellar ataxia 3: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATX3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.

Wikipedia : 74 Machado-Joseph disease (MJD), also known as Machado-Joseph Azorean disease, Machado's disease, Joseph's... more...

GeneReviews: NBK1196

Related Diseases for Machado-Joseph Disease

Diseases in the Machado-Joseph Disease family:

Machado-Joseph Disease Type 1 Machado-Joseph Disease Type 3
Machado-Joseph Disease Type 2

Diseases related to Machado-Joseph Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 196)
# Related Disease Score Top Affiliating Genes
1 olivopontocerebellar atrophy 32.7 SNCA SLC6A3 RPS27A CACNA1A ATXN7 ATXN2
2 spinocerebellar degeneration 32.6 ATXN3 ATXN2 ATXN1
3 spinocerebellar ataxia 2 32.0 HTT CACNA1A ATXN8OS ATXN7 ATXN3 ATXN2
4 spinocerebellar ataxia 1 31.7 TBP HTT CACNA1A ATXN8OS ATXN7 ATXN3
5 parkinsonism 31.6 SNCA SLC6A3 ATXN2
6 sleep disorder 31.5 SNCA SLC6A3 HTR1A ATXN3
7 rem sleep behavior disorder 31.4 SNCA SLC6A3 RPS27A PRKN
8 muscular atrophy 31.2 SNCA HTT ATXN3 ATXN1
9 autosomal dominant cerebellar ataxia 31.1 VCP TBP SNCA RPS27A PRKN LOC108663987
10 dystonia 31.0 TBP SLC6A3 PRKN HTT CACNA1A ATXN7
11 multiple system atrophy 1 30.9 SNCA SLC6A3 RPS27A PRKN HTT ATXN1
12 movement disease 30.8 SNCA SLC6A3 PRKN HTT CACNA1A
13 huntington disease 30.7 TBP SNCA HTT BECN1 ATXN7 ATXN3
14 motor neuron disease 30.7 VCP SNCA RPS27A PRKN HTT HTR1A
15 spinocerebellar ataxia 8 30.6 HTT ATXN8OS ATXN7 ATXN2 ATXN1
16 restless legs syndrome 30.6 TBP SNCA SLC6A3 PRKN LOC108663987 CACNA1A
17 episodic ataxia 30.6 CACNA1A ATXN7 ATXN1
18 dentatorubral-pallidoluysian atrophy 30.5 TBP SNCA PRKN HTT CACNA1A ATXN8OS
19 episodic ataxia, type 2 30.5 CACNA1A ATXN7 ATXN2 ATXN1
20 friedreich ataxia 30.5 TBP CACNA1A ATXN8OS ATXN3 ATXN2 ATXN1
21 amyotrophic lateral sclerosis 1 30.5 VCP SNCA SLC6A3 RPS27A PRKN HTT
22 spinocerebellar ataxia 10 30.5 ATXN8OS ATXN7 ATXN3 ATXN2 ATN1
23 hereditary ataxia 30.5 TBP CACNA1A ATXN8OS ATXN7 ATXN3 ATXN2
24 spinocerebellar ataxia 6 30.3 TBP CACNA1A ATXN8OS ATXN7 ATXN3 ATXN2
25 parkinson disease, late-onset 30.1 VCP TBP SNCA SLC6A3 RPS27A PRKN
26 choreatic disease 29.9 TBP SNCA SLC6A3 PRKN HTT CACNA1A
27 spinocerebellar ataxia 7 29.9 TBP HTT ATXN8OS ATXN7 ATXN3 ATXN2
28 dementia 29.8 VCP SNCA SLC6A3 RPS27A PRKN HTT
29 cerebellar disease 29.6 TBP SNCA PRKN HTT CACNA1A ATXN8OS
30 spinocerebellar ataxia, autosomal recessive 3 11.3
31 spinocerebellar ataxia, x-linked 3 11.3
32 machado-joseph disease type 1 11.3
33 machado-joseph disease type 3 11.3
34 machado-joseph disease type 2 11.3
35 spinocerebellar atrophy 11.3
36 ataxia and polyneuropathy, adult-onset 11.3
37 ataxias and cerebellar or spinocerebellar degeneration 11.2
38 mohr-tranebjaerg syndrome 11.2
39 spinocerebellar atrophy with pupillary paralysis 11.0
40 brachydactylous dwarfism mseleni type 10.9
41 dystonia 11, myoclonic 10.9
42 spinocerebellar ataxia 18 10.9
43 neuropathy 10.8
44 kearns-sayre syndrome 10.7
45 pathologic nystagmus 10.7
46 peripheral nervous system disease 10.7
47 spasticity 10.7
48 chronic progressive external ophthalmoplegia 10.5
49 polyneuropathy 10.5
50 autonomic dysfunction 10.5

Graphical network of the top 20 diseases related to Machado-Joseph Disease:



Diseases related to Machado-Joseph Disease

Symptoms & Phenotypes for Machado-Joseph Disease

Human phenotypes related to Machado-Joseph Disease:

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001347
2 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
3 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
4 diplopia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000651
5 dysarthria 58 31 very rare (1%) Very frequent (99-80%) HP:0001260
6 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
7 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
8 progressive external ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000590
9 proptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000520
10 abnormality of extrapyramidal motor function 58 31 hallmark (90%) Very frequent (99-80%) HP:0002071
11 dystonia 58 31 very rare (1%) Very frequent (99-80%) HP:0001332
12 clumsiness 58 31 hallmark (90%) Very frequent (99-80%) HP:0002312
13 progressive cerebellar ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002073
14 abnormality of temperature regulation 58 31 occasional (7.5%) Occasional (29-5%) HP:0004370
15 vocal cord paralysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001605
16 vestibular dysfunction 58 31 occasional (7.5%) Occasional (29-5%) HP:0001751
17 abnormal autonomic nervous system physiology 31 occasional (7.5%) HP:0012332
18 spasticity 31 very rare (1%) HP:0001257
19 ataxia 31 very rare (1%) HP:0001251
20 fasciculations 31 very rare (1%) HP:0002380
21 external ophthalmoplegia 31 very rare (1%) HP:0000544
22 parkinsonism 31 very rare (1%) HP:0001300
23 gaze-evoked nystagmus 31 very rare (1%) HP:0000640
24 ptosis 31 HP:0000508
25 dysphagia 31 HP:0002015
26 impaired vibratory sensation 31 HP:0002495
27 babinski sign 31 HP:0003487
28 cerebellar atrophy 31 HP:0001272
29 rigidity 31 HP:0002063
30 dementia 31 HP:0000726
31 muscle spasm 31 HP:0003394
32 distal amyotrophy 31 HP:0003693
33 spinocerebellar tract degeneration 31 HP:0002503
34 postural instability 31 HP:0002172
35 limb ataxia 31 HP:0002070
36 urinary bladder sphincter dysfunction 31 HP:0002839
37 truncal ataxia 31 HP:0002078
38 bradykinesia 31 HP:0002067
39 absent achilles reflex 31 HP:0003438
40 supranuclear ophthalmoplegia 31 HP:0000623
41 gliosis 31 HP:0002171
42 chronic pain 31 HP:0012532
43 dilated fourth ventricle 31 HP:0002198
44 dysmetric saccades 31 HP:0000641
45 impaired horizontal smooth pursuit 31 HP:0001151
46 facial-lingual fasciculations 31 HP:0007089
47 abnormal electrooculogram 31 HP:0030454

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
spasticity
dysarthria
rigidity
spinocerebellar tract degeneration
postural instability
more
Abdomen Gastrointestinal:
dysphagia

Muscle Soft Tissue:
fasciculations
muscle cramps

Head And Neck Eyes:
diplopia
external ophthalmoplegia
supranuclear ophthalmoplegia
gaze-evoked nystagmus
dysmetric saccades
more
Neurologic Peripheral Nervous System:
peripheral neuropathy
decreased vibration sense
impaired thermal sense
decreased or absent ankle reflexes
distal muscular atrophy

Genitourinary Bladder:
sphincter disturbances

Clinical features from OMIM®:

109150 (Updated 05-Mar-2021)

UMLS symptoms related to Machado-Joseph Disease:


ataxia, abnormality of extrapyramidal motor function, bradykinesia, chronic pain, muscular fasciculation, muscle cramp, muscle rigidity, muscle spasticity, cerebellar ataxia, ataxia, truncal, abnormal pyramidal signs

MGI Mouse Phenotypes related to Machado-Joseph Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.35 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 BECN1
2 growth/size/body region MP:0005378 10.25 ATN1 ATXN1 ATXN2 ATXN7 BECN1 CACNA1A
3 homeostasis/metabolism MP:0005376 10.25 ATN1 ATXN1 ATXN2 ATXN3 BECN1 CACNA1A
4 mortality/aging MP:0010768 10.18 ATN1 ATXN1 ATXN2 ATXN7 BECN1 CACNA1A
5 nervous system MP:0003631 10.17 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 BECN1
6 cardiovascular system MP:0005385 10.16 ATN1 BECN1 HSPB1 HTR1A HTT PRKN
7 no phenotypic analysis MP:0003012 9.91 ATN1 CACNA1A HSPB1 HTR1A HTT PRKN
8 normal MP:0002873 9.76 ATN1 BECN1 CACNA1A HSPB1 HTT PRKN
9 reproductive system MP:0005389 9.61 ATN1 ATXN2 ATXN7 BECN1 CACNA1A HTT
10 skeleton MP:0005390 9.28 ATXN1 ATXN7 BECN1 HTT PRKN SLC6A3

Drugs & Therapeutics for Machado-Joseph Disease

Drugs for Machado-Joseph Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lithium carbonate Approved Phase 2, Phase 3 554-13-2
2
Glutamic acid Approved, Nutraceutical Phase 3 56-86-0 33032
3 Psychotropic Drugs Phase 2, Phase 3
4 Antidepressive Agents Phase 2, Phase 3
5
Varenicline Approved, Investigational Phase 2 249296-44-4 5310966
6
Menthol Approved Phase 2 2216-51-5 16666
7 Nicotinic Agonists Phase 2
8 Neurotransmitter Agents Phase 2
9 Cholinergic Agents Phase 2
10
4-Aminopyridine Approved 504-24-5 1727
11 Potassium Channel Blockers

Interventional clinical trials:

(show all 27)
# Name Status NCT ID Phase Drugs
1 Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3 Completed NCT01096082 Phase 2, Phase 3 Lithium Carbonate;Placebo
2 An Open Pilot Trial of BHV-4157 in Adult Subjects With Cerebellar Ataxia Active, not recruiting NCT03408080 Phase 3 BHV-4157
3 A Phase III, Long-Term, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Subjects With Spinocerebellar Ataxia. Active, not recruiting NCT03701399 Phase 3 troriluzole;Placebos
4 The Influence of Deep Repetitive Transcranial Magnetic Stimulation (TMS) on Cerebellar Signs in Patients With Spinocerebellar Ataxia Type 3 (SCA3 - Machado Joseph Disease) Completed NCT02039206 Phase 2
5 A Pilot, Randomized, Double-blind, Placebo-controlled Phase I Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3 Completed NCT00992771 Phase 2 varenicline;placebo
6 A Single-Center, Randomized, Double-Blind, Parallel-Group, Dose-Controlled Study, to Assess Safety, Tolerability and Efficacy of Intravenous Cabaletta® in Patients With Machado-Joseph Disease Completed NCT02147886 Phase 2 Cabaletta for IV infusion once weekly during 24 weeks;Cabaletta for IV infusion once weekly during 24 weeks
7 A Clinical Research on the Safety/Efficacy of Umbilical Cord Mesenchymal Stem Cells Therapy for Patients With Spinocerebellar Ataxia Not yet recruiting NCT03378414 Phase 2
8 Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of CAD-1883 in Adults With Spinocerebellar Ataxia (Synchrony-1) Suspended NCT04301284 Phase 2 CAD-1883;Placebos
9 Phenylbutyrate in SCA3: a Double-blind, Placebo-controlled Study to Determine Safety and Efficacy of Sodium Phenylbutyrate in Patients With SCA3 Withdrawn NCT01096095 Phase 2 Placebo;Sodium Phenylbutyrate
10 Machado-Joseph Disease in Israel: Clinical Phenotype and Genotype of a Jew Yemenite Subpopulation Unknown status NCT02175290
11 Prospective Study of Individuals at Risk for Spinocerebellar Ataxia Type 1, Type 2, Type 3, Type 6 and Type 7 (SCA1, SCA2, SCA3, SCA6, SCA7) Unknown status NCT01037777
12 Clinical Effects of Oral Trehalose In Patients With Spinocerebellar Ataxia 3: A Pilot Study Completed NCT04426149
13 Weight in Lower Limbs Improves Gait Ataxia Of in Machado-Joseph Disease Patients: A Randomized Crossover Trial Completed NCT02906046
14 Therapeutic Effect of Dalfampridine on Gait Incoordination in Spinocerebellar Ataxias- A Randomized, Double-blinded, Placebo-controlled, Crossover Clinical Trial Completed NCT01811706 Dalfampridine;Placebo
15 Rehabilitative Trial With Cerebello-Spinal tDCS for the Treatment of Neurodegenerative Ataxia Completed NCT03120013
16 The Investigation of the Pre-movement Facilitation of Agonist-antagonist Muscles and the Effect of the Feedforward Rehabilitation in Individuals With Hypermetria Completed NCT01983670
17 Clinical Trial Readiness for SCA1 and SCA3 Recruiting NCT03487367
18 A Randomised Controlled Trial on the Clinical Efficacy of Oral Trehalose in Patients With Spinocerebellar Ataxia 3: Clinical & FMRI Correlation Recruiting NCT04399265
19 Neuropsychiatry and Cognition in the Context of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD) Recruiting NCT04714307
20 Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) to Study Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias (SCA) Recruiting NCT01060371
21 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
22 APDM Instrumented Data Exchange for Ataxia (IDEA) Study Recruiting NCT04268147
23 Identification of Biomarkers in Spinocerebellar Ataxia 3 Active, not recruiting NCT03885167
24 Natural History of Oculomotor Neurophysiology in Ataxic and Pre-ataxic Carriers of Machado-Joseph Disease/Spinocerebellar Ataxia Type 3 (SCA3/MJD) Active, not recruiting NCT04229823
25 Biomarkers and Genetic Modifiers in a Study of Pre-ataxic and Ataxic SCA3/MJD Carriers (BIGPRO Study) - Astrocytes Active, not recruiting NCT04419974
26 Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxias: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase Active, not recruiting NCT04153110
27 The Effect of Functional Trunk Training on Trunk Control and Upper Extremity Functions in Hereditary Ataxia Patients With Autosomal Recessive Active, not recruiting NCT04740359

Search NIH Clinical Center for Machado-Joseph Disease

Cochrane evidence based reviews: machado-joseph disease

Genetic Tests for Machado-Joseph Disease

Genetic tests related to Machado-Joseph Disease:

# Genetic test Affiliating Genes
1 Azorean Disease 29 ATXN3

Anatomical Context for Machado-Joseph Disease

MalaCards organs/tissues related to Machado-Joseph Disease:

40
Eye, Tongue, Cerebellum, Spinal Cord, Brain, Skeletal Muscle, Cortex

Publications for Machado-Joseph Disease

Articles related to Machado-Joseph Disease:

(show top 50) (show all 1511)
# Title Authors PMID Year
1
CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. 6 57 25 61
7874163 1994
2
Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. 57 25 61 54
8619527 1996
3
Chronic pain in Machado-Joseph disease: a frequent and disabling symptom. 25 57 61
18071041 2007
4
Survival estimates for patients with Machado-Joseph disease (SCA3). 61 57 25
17894834 2007
5
Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort. 25 57 61
15747371 2005
6
Autonomic dysfunction in Machado-Joseph disease. 57 61 25
15824264 2005
7
Cognitive impairments in Machado-Joseph disease. 61 25 57
15534186 2004
8
Haplotype study in Dutch SCA3 and SCA6 families: evidence for common founder mutations. 61 57 25
15026782 2004
9
Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype. 25 57 61
11409435 2001
10
Ancestral origins of the Machado-Joseph disease mutation: a worldwide haplotype study. 25 61 57
11133357 2001
11
Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. 57 61 25
8931575 1996
12
Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus. 61 57 25
7573040 1995
13
Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorena Portuguese family. 25 61 57
7189034 1980
14
Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3? 61 57 54
20308049 2010
15
Proteotoxic stress increases nuclear localization of ataxin-3. 57 54 61
19843543 2010
16
Reversibility of symptoms in a conditional mouse model of spinocerebellar ataxia type 3. 54 61 57
19666958 2009
17
Segregation distortion of wild-type alleles at the Machado-Joseph disease locus: a study in normal families from the Azores islands (Portugal). 57 54 61
18286225 2008
18
Dementia and delirium in 4 patients with Machado-Joseph disease. 57 61 54
12433269 2002
19
Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. 61 54 57
11939898 2002
20
High level expression of expanded full-length ataxin-3 in vitro causes cell death and formation of intranuclear inclusions in neuronal cells. 57 54 61
10369861 1999
21
Expanded CAG repeats in spinocerebellar ataxia (SCA1) segregate with distinct haplotypes in South african families. 57 54 61
9225982 1997
22
Non-Mendelian transmission at the Machado-Joseph disease locus in normal females: preferential transmission of alleles with smaller CAG repeats. 57 61 54
9132496 1997
23
Evidence for inter-generational instability in the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. 54 57 61
8528200 1995
24
CAG Repeat Size Influences the Progression Rate of Spinocerebellar Ataxia Type 3. 57 61
32978817 2021
25
Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease. 57 61
26373603 2015
26
Chinese homozygous Machado-Joseph disease (MJD)/SCA3: a case report. 57 61
25566755 2015
27
Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. 61 57
22113611 2011
28
Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history? 61 57
19329990 2009
29
Motor nerve hyperexcitability and muscle cramps in Machado-Joseph disease. 57 61
19139316 2009
30
Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease. 57 61
18385100 2008
31
Muscle excitability abnormalities in Machado-Joseph disease. 57 61
18413477 2008
32
Machado-Joseph disease enhances genetic fitness: a comparison between affected and unaffected women and between MJD and the general population. 61 57
17683516 2008
33
Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families. 61 57
17805477 2007
34
Proteolytic cleavage of polyglutamine-expanded ataxin-3 is critical for aggregation and sequestration of non-expanded ataxin-3. 61 57
16407371 2006
35
Ribosomal frameshifting on MJD-1 transcripts with long CAG tracts. 61 57
16087686 2005
36
Founder haplotype for Machado-Joseph disease in the Indian population: novel insights from history and polymorphism studies. 57 61
15824265 2005
37
Was the ataxia of Pierre Marie Machado-Joseph disease?: A reappraisal based on the last autopsy case from la Salpêtrière Hospital. 61 57
15148161 2004
38
Peripheral nerve involvement in spinocerebellar ataxias. 61 57
14967775 2004
39
Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families. 57 61
15480876 2004
40
Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients. 61 57
12810491 2003
41
Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis. 61 57
11889231 2002
42
Improvement in the molecular diagnosis of Machado-Joseph disease. 61 57
11708990 2001
43
Spinocerebellar ataxia type 3 phenotypically resembling parkinson disease in a black family. 57 61
11176969 2001
44
Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia. 61 57
11186889 2000
45
CAG tract of MJD-1 may be prone to frameshifts causing polyalanine accumulation. 61 57
10942424 2000
46
Ataxin-3 with an altered conformation that exposes the polyglutamine domain is associated with the nuclear matrix. 61 57
10556285 1999
47
French Machado-Joseph disease patients do not exhibit gametic segregation distortion: a sperm typing analysis. 61 57
10441343 1999
48
Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. 57 61
10525976 1999
49
Machado-Joseph disease presenting as severe generalised dystonia in a German patient. 57 61
10525985 1999
50
Cluster of Machado-Joseph disease in a small rural town near Nagasaki City, Japan: clinical and genetic studies of two families. 57 61
10399876 1999

Variations for Machado-Joseph Disease

ClinVar genetic disease variations for Machado-Joseph Disease:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LOC108663987 NM_004993.5(ATXN3):c.886_888CAG(60_86) (p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) Microsatellite Pathogenic 209995 14:92537382-92537384 14:92071038-92071040
2 LOC108663987 NM_004993.5(ATXN3):c.892CAG[(8_36)] Microsatellite Pathogenic 3551 14:92537355-92537357 14:92071011-92071013
3 LOC108663987 NM_004993.6(ATXN3):c.892CAG[12] (p.Gln302_Gln305dup) Microsatellite Benign 931861 14:92537354-92537355 14:92071010-92071011
4 ATXN3 NM_004993.6(ATXN3):c.916G>C (p.Gly306Arg) SNV Benign 128515 rs12895357 14:92537354-92537354 14:92071010-92071010
5 LOC108663987 NM_004993.5(ATXN3):c.886_888CAG(12_44) (p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) Microsatellite Benign 209994 14:92537382-92537384 14:92071038-92071040

Expression for Machado-Joseph Disease

Search GEO for disease gene expression data for Machado-Joseph Disease.

Pathways for Machado-Joseph Disease

Pathways related to Machado-Joseph Disease according to KEGG:

36
# Name Kegg Source Accession
1 Spinocerebellar ataxia hsa05017
2 Protein processing in endoplasmic reticulum hsa04141

Pathways related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.59 VCP USP2 SNCA RPS27A PRKN BECN1
2
Show member pathways
13.11 VCP TBP SNCA SLC6A3 RPS27A PRKN
3
Show member pathways
12.64 VCP USP2 RPS27A PRKN BECN1 ATXN7
4
Show member pathways
12.47 SNCA SLC6A3 PRKN HSPB1 ATXN7 ATXN3
5 12.38 SNCA RPS27A PRKN HTT HTR1A ATXN1
6 11.99 VCP PRKN ATXN3L ATXN3
7
Show member pathways
11.67 VCP HSPB1 ATXN3
8 11.63 SNCA SLC6A3 PRKN ATXN2
9 11.49 RPS27A PRKN BECN1
10 11.38 TBP CACNA1A BECN1 ATXN8OS ATXN3L ATXN3
11 11.11 SNCA SLC6A3 PRKN
12 10.43 VCP RPS27A PRKN ATXN3L ATXN3

GO Terms for Machado-Joseph Disease

Cellular components related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 10.21 VCP SNCA RPS27A PRKN HTT HSPB1
2 nucleus GO:0005634 10.13 VCP USP2 TBP SNCA RPS27A PRKN
3 cytoplasm GO:0005737 9.86 VCP USP2 TBP SNCA SLC6A3 RPS27A
4 synapse GO:0045202 9.85 VCP SNCA PRKN HTR1A CACNA1A ATXN3
5 protein-containing complex GO:0032991 9.8 VCP TBP SNCA PRKN HTT BECN1
6 nuclear matrix GO:0016363 9.46 ATXN7 ATXN3 ATXN1 ATN1
7 nuclear inclusion body GO:0042405 9.4 ATXN3 ATXN1
8 perinuclear region of cytoplasm GO:0048471 9.17 VCP USP2 SNCA PRKN HTT ATXN2

Biological processes related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.97 USP2 SNCA RPS27A PRKN ATXN1 ATN1
2 ubiquitin-dependent protein catabolic process GO:0006511 9.88 VCP USP2 PRKN ATXN3
3 chemical synaptic transmission GO:0007268 9.81 SNCA HTR1A CACNA1A ATXN3
4 macroautophagy GO:0016236 9.71 VCP PRKN BECN1
5 regulation of neurotransmitter secretion GO:0046928 9.58 SNCA PRKN
6 dopamine metabolic process GO:0042417 9.57 SNCA PRKN
7 ERAD pathway GO:0036503 9.56 VCP PRKN
8 proteasomal protein catabolic process GO:0010498 9.55 VCP PRKN
9 synaptic transmission, dopaminergic GO:0001963 9.52 SNCA PRKN
10 exploration behavior GO:0035640 9.48 HTR1A ATXN3
11 dopamine biosynthetic process GO:0042416 9.46 SNCA SLC6A3
12 mitophagy GO:0000423 9.43 PRKN BECN1
13 protein destabilization GO:0031648 9.43 SNCA PRKN HTT
14 positive regulation of autophagy of mitochondrion GO:1903599 9.4 PRKN HTT
15 aggresome assembly GO:0070842 9.37 VCP PRKN
16 regulation of dopamine metabolic process GO:0042053 9.33 SLC6A3 PRKN HTR1A
17 response to iron(II) ion GO:0010040 9.32 SNCA BECN1
18 protein deubiquitination GO:0016579 9.23 VCP USP2 RPS27A PRKN BECN1 ATXN7
19 dopamine uptake involved in synaptic transmission GO:0051583 9.13 SNCA SLC6A3 PRKN

Molecular functions related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.61 VCP USP2 SNCA PRKN HTT HSPB1
2 thiol-dependent ubiquitin-specific protease activity GO:0004843 9.43 USP2 ATXN3L ATXN3
3 phospholipase binding GO:0043274 9.16 SNCA PRKN
4 ubiquitin protein ligase binding GO:0031625 9.1 VCP USP2 RPS27A PRKN BECN1 ATXN3

Sources for Machado-Joseph Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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