SPG3A
MCID: SPS215
MIFTS: 61

Spastic Paraplegia 3, Autosomal Dominant (SPG3A)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Spastic Paraplegia 3, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 3, Autosomal Dominant:

Name: Spastic Paraplegia 3, Autosomal Dominant 56 73 71
Strumpell Disease 56 12 58 73
Spg3a 56 12 73 54
Spastic Paraplegia 3a, Autosomal Dominant 56 29 13
Fsp1 56 12 73
Autosomal Dominant Spastic Paraplegia Type 3 12 58
Hereditary Spastic Paraplegia 3a 12 15
Spg3 56 73
Familial Spastic Paraplegia, Autosomal Dominant, 1; Fsp1 56
Familial Spastic Paraplegia, Autosomal Dominant, 1 56
Autosomal Dominant Familial Spastic Paraplegia 1 12
Familial Spastic Paraplegia Autosomal Dominant 1 73
Paraplegia, Spastic, Autosomal Dominant, Type 3a 39
Autosomal Dominant Spastic Paraplegia 3 12
Spastic Paraplegia, Hereditary 71
Strumpell-Lorrain Syndrome 73

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant spastic paraplegia type 3
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Portugal),1-9/1000000 (Europe); Age of onset: Adult,Childhood;

OMIM:

56
Miscellaneous:
insidious onset
genetic heterogeneity
reduced penetrance
highly variable severity
usually shows early age at onset (range 1 to 7 years, mean 4.6 years)
later onset has been rarely reported (up to age 68 years)
most patients need assistance walking or are wheelchair-bound
variable progression

Inheritance:
autosomal dominant


HPO:

31
spastic paraplegia 3, autosomal dominant:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course variable expressivity incomplete penetrance insidious onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110791
OMIM 56 182600
OMIM Phenotypic Series 56 PS303350
MeSH 43 D015419
ICD10 32 G11.4
MESH via Orphanet 44 C536864
ICD10 via Orphanet 33 G11.4
UMLS via Orphanet 72 C2931355
Orphanet 58 ORPHA100984
UMLS 71 C0037773 C2931355

Summaries for Spastic Paraplegia 3, Autosomal Dominant

OMIM : 56 The hereditary spastic paraplegias are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). SPG is classified according to both the mode of inheritance (autosomal dominant, autosomal recessive (see 270800), and X-linked (see 303350)) and whether progressive spasticity occurs in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness. The major neuropathologic feature of autosomal dominant, uncomplicated SPG is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). Spinocerebellar fibers are involved to a lesser extent. Since the description of 'pure' hereditary spastic paraparesis of late onset by Strumpell (1904), many 'complicated' forms of the disorder have been reported and the question as to whether a 'pure' form exists has been raised off and on. Probably in large part because of their exceptional length, the pyramidal tracts are unusually vulnerable to both acquired and genetic derangement. Although a majority of reported families have displayed recessive inheritance, 10 to 30% of families have a dominant pattern and in fact recessive inheritance of a 'pure' spastic paraplegia may be rare. (182600)

MalaCards based summary : Spastic Paraplegia 3, Autosomal Dominant, also known as strumpell disease, is related to spastic paraplegia 4, autosomal dominant and spastic paraplegia 20, autosomal recessive, and has symptoms including urgency of micturition, pain in lower limb and leg cramps. An important gene associated with Spastic Paraplegia 3, Autosomal Dominant is ATL1 (Atlastin GTPase 1), and among its related pathways/superpathways are ERK Signaling and Wnt / Hedgehog / Notch. The drugs Acetylcholine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include tongue, cortex and spinal cord, and related phenotypes are babinski sign and lower limb spasticity

Disease Ontology : 12 A hereditary spastic paraplegia that is characterized by lower limb weakness and spasticity that is generally non-progressive or extremely slow and has material basis in mutation in the ATL1 gene on chromosome 14q22.

UniProtKB/Swiss-Prot : 73 Spastic paraplegia 3, autosomal dominant: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.

Related Diseases for Spastic Paraplegia 3, Autosomal Dominant

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23, Autosomal Recessive Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Recessive
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Spastic Paraplegia 80, Autosomal Dominant
Hereditary Spastic Paraplegia 23 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 10
Spastic Paraplegia 12 Spastic Paraplegia 13
Spastic Paraplegia 14 Spastic Paraplegia 15
Spastic Paraplegia 16 Spastic Paraplegia 17
Spastic Paraplegia 18 Spastic Paraplegia 19
Spastic Paraplegia 24 Spastic Paraplegia 25
Spastic Paraplegia 26 Spastic Paraplegia 29
Spastic Paraplegia 3 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Spastic Paraplegia Type 49 Autosomal Recessive Spastic Paraplegia Type 60
Autosomal Recessive Spastic Paraplegia Type 59 Autosomal Recessive Spastic Paraplegia Type 69
Autosomal Recessive Spastic Paraplegia Type 70 Autosomal Recessive Spastic Paraplegia Type 71
Autosomal Recessive Spastic Paraplegia Type 66 Autosomal Recessive Spastic Paraplegia Type 67
Autosomal Dominant Spastic Paraplegia Type 9b

Diseases related to Spastic Paraplegia 3, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 94)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 4, autosomal dominant 32.7 SPG11 SPAST RTN2 REEP1 ATL1
2 spastic paraplegia 20, autosomal recessive 32.5 SPG11 SPAST ATL1
3 spastic paraplegia 8, autosomal dominant 32.3 SPG11 SPAST REEP1 ATL1
4 spastic paraplegia 2, x-linked 32.1 SPG11 SPAST RTN2 REEP1 ATL1
5 spastic paraplegia 12, autosomal dominant 32.1 SPG11 SPAST RTN2 REEP1 ATL1
6 paraplegia 31.6 SPG11 SPAST RTN2 REEP1 ATL1
7 spastic paraplegia 13, autosomal dominant 30.6 SPAST RTN2 REEP1 ATL1
8 amyotrophic lateral sclerosis 1 29.9 TJP1 SPG11 SPAST FN1 CDH2 CDH1
9 hereditary spastic paraplegia 29.7 TJP1 THY1 TBX1 SPG11 SPAST SNAI2
10 spondyloarthropathy 1 11.6
11 spastic paraplegia 3a 11.5
12 spastic paraplegia 3 11.5
13 spastic paraplegia 9a, autosomal dominant 11.2
14 neuropathy, hereditary sensory, type id 11.2
15 spastic paraplegia 72, autosomal recessive 11.2
16 spastic paraplegia 80, autosomal dominant 11.2
17 spastic paraplegia 4 10.7
18 spasticity 10.7
19 spastic paraplegia 33, autosomal dominant 10.5 SPAST REEP1 ATL1
20 spastic paraplegia 16, x-linked 10.5 SPG11 SPAST
21 pauci-immune glomerulonephritis 10.5 SMAD2 CCN2
22 adenoid squamous cell carcinoma 10.5 PECAM1 CDH1
23 spastic paraplegia 14, autosomal recessive 10.5 SPG11 SPAST
24 autosomal dominant non-syndromic intellectual disability 9 10.5 RTN2 REEP1
25 spastic paraplegia 53, autosomal recessive 10.4 RTN2 ATL1
26 pure hereditary spastic paraplegia 10.4 SPAST RTN2 ATL1
27 spastic paraplegia 26, autosomal recessive 10.4 SPG11 SPAST REEP1
28 spastic paraplegia 18, autosomal recessive 10.4 SPG11 REEP1
29 epithelioid sarcoma 10.4 PECAM1 CDH5 CDH1
30 spastic paraplegia 28, autosomal recessive 10.4 SPG11 REEP1
31 spastic paraplegia 5a, autosomal recessive 10.4 SPG11 SPAST
32 exudative vitreoretinopathy 1 10.4 PECAM1 FN1 CDH5
33 luminal breast carcinoma 10.4 SNAI2 SNAI1 CDH1
34 kidney hypertrophy 10.4 FN1 CCN2
35 spastic paraplegia 54, autosomal recessive 10.4 SPG11 REEP1
36 hereditary spastic paraplegia 51 10.4 SPG11 RTN2
37 spastic paraplegia 30, autosomal recessive 10.4 SPG11 SPAST REEP1 ATL1
38 spastic paraplegia 6, autosomal dominant 10.4 SPG11 SPAST REEP1 ATL1
39 vitreoretinopathy, neovascular inflammatory 10.4 TJP1 FN1 CCN2
40 spastic paraplegia 15, autosomal recessive 10.4 SPG11 SPAST REEP1 ATL1
41 spastic paraplegia 17, autosomal dominant 10.4 SPG11 SPAST REEP1 ATL1
42 spastic paraplegia 61, autosomal recessive 10.4 SPAST RTN2 REEP1 ATL1
43 idiopathic interstitial pneumonia 10.4 SMAD2 FN1 CCN2
44 spastic paraplegia 52, autosomal recessive 10.4 SPG11 RTN2
45 neuropathy, hereditary sensory, type iic 10.3 SPG11 RTN2 REEP1
46 glioblastoma classical subtype 10.3 SNAI2 SNAI1
47 axonal neuropathy 10.3
48 neuropathy 10.3
49 spindle cell carcinoma 10.3 SNAI2 SNAI1 CDH2 CDH1
50 spastic paraplegia 57, autosomal recessive 10.3 SPG11 REEP1

Graphical network of the top 20 diseases related to Spastic Paraplegia 3, Autosomal Dominant:



Diseases related to Spastic Paraplegia 3, Autosomal Dominant

Symptoms & Phenotypes for Spastic Paraplegia 3, Autosomal Dominant

Human phenotypes related to Spastic Paraplegia 3, Autosomal Dominant:

58 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
2 lower limb spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002061
3 distal lower limb muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0009053
4 lower limb hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002395
5 ankle clonus 58 31 frequent (33%) Frequent (79-30%) HP:0011448
6 spastic gait 58 31 frequent (33%) Frequent (79-30%) HP:0002064
7 distal lower limb amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0008944
8 toe walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0040083
9 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
10 urinary urgency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000012
11 impaired vibratory sensation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002495
12 intellectual disability, mild 31 occasional (7.5%) HP:0001256
13 hypoplasia of the corpus callosum 31 occasional (7.5%) HP:0002079
14 dysarthria 58 31 very rare (1%) Very rare (<4-1%) HP:0001260
15 growth delay 58 31 very rare (1%) Very rare (<4-1%) HP:0001510
16 rigidity 58 31 very rare (1%) Very rare (<4-1%) HP:0002063
17 bradykinesia 58 31 very rare (1%) Very rare (<4-1%) HP:0002067
18 frequent falls 58 31 very rare (1%) Very rare (<4-1%) HP:0002359
19 lower limb hypertonia 58 31 very rare (1%) Very rare (<4-1%) HP:0006895
20 hyperesthesia 58 31 very rare (1%) Very rare (<4-1%) HP:0100963
21 hyperreflexia 31 HP:0001347
22 scoliosis 31 HP:0002650
23 gait disturbance 58 Frequent (79-30%)
24 peripheral neuropathy 58 Occasional (29-5%)
25 pes cavus 31 HP:0001761
26 urinary bladder sphincter dysfunction 31 HP:0002839
27 spastic paraplegia 31 HP:0001258
28 lower limb muscle weakness 31 HP:0007340
29 impaired vibration sensation in the lower limbs 31 HP:0002166
30 degeneration of the lateral corticospinal tracts 31 HP:0002314
31 urinary incontinence 31 HP:0000020
32 paraplegia 31 HP:0010550

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
lower limb spasticity
spastic gait
delayed motor development
extensor plantar responses
more
Neurologic Peripheral Nervous System:
degeneration of the lateral corticospinal tracts
decreased vibratory sense in lower limbs after long disease duration

Skeletal Feet:
pes cavus in patients with early onset

Skeletal Spine:
scoliosis

Genitourinary Bladder:
urinary urgency
urinary incontinence
sphincter disturbances

Clinical features from OMIM:

182600

UMLS symptoms related to Spastic Paraplegia 3, Autosomal Dominant:


urgency of micturition, pain in lower limb, leg cramps

GenomeRNAi Phenotypes related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Multipolar spindles GR00222-A-1 8.8 CDH5 POSTN SNAI1

MGI Mouse Phenotypes related to Spastic Paraplegia 3, Autosomal Dominant:

45 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.41 CCN2 CDH1 CDH2 CDH5 DDR2 FN1
2 cardiovascular system MP:0005385 10.34 CCN2 CDH1 CDH2 CDH5 DDR2 FN1
3 growth/size/body region MP:0005378 10.25 CCN2 CDH1 CDH2 CDH5 DDR2 FN1
4 homeostasis/metabolism MP:0005376 10.25 CCN2 CDH1 CDH2 CDH5 DDR2 FN1
5 embryo MP:0005380 10.16 CCN2 CDH1 CDH2 CDH5 FN1 SMAD2
6 craniofacial MP:0005382 10.15 CCN2 CDH5 DDR2 FN1 POSTN SMAD2
7 mortality/aging MP:0010768 10.13 CCN2 CDH1 CDH2 CDH5 DDR2 FN1
8 digestive/alimentary MP:0005381 10.02 CCN2 CDH1 PECAM1 SMAD2 SNAI1 SNAI2
9 integument MP:0010771 9.97 CCN2 CDH1 CDH5 DDR2 FN1 SMAD2
10 nervous system MP:0003631 9.93 CDH2 DDR2 FN1 REEP1 SMAD2 SNAI1
11 neoplasm MP:0002006 9.73 CDH1 DDR2 FN1 POSTN S100A4 SMAD2
12 normal MP:0002873 9.7 CCN2 CDH1 CDH5 FN1 S100A4 SMAD2
13 skeleton MP:0005390 9.32 CCN2 DDR2 FN1 PECAM1 POSTN REEP1

Drugs & Therapeutics for Spastic Paraplegia 3, Autosomal Dominant

Drugs for Spastic Paraplegia 3, Autosomal Dominant (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 33)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational Phase 2, Phase 3 51-84-3 187
2 Neurotransmitter Agents Phase 2, Phase 3
3 Acetylcholine Release Inhibitors Phase 2, Phase 3
4 Botulinum Toxins Phase 2, Phase 3
5 Cholinergic Agents Phase 2, Phase 3
6
Atorvastatin Approved Phase 2 134523-00-5 60823
7
Resveratrol Approved, Experimental, Investigational Phase 2 501-36-0 445154
8
chenodeoxycholic acid Approved Phase 2 474-25-9 10133
9
Evolocumab Approved Phase 1, Phase 2 1256937-27-5
10 Cathartics Phase 2
11 Anti-Inflammatory Agents Phase 2
12 Gastrointestinal Agents Phase 2
13 Anti-Inflammatory Agents, Non-Steroidal Phase 2
14 Antioxidants Phase 2
15 Platelet Aggregation Inhibitors Phase 2
16 Analgesics, Non-Narcotic Phase 2
17 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 2
18 Laxatives Phase 2
19 Antirheumatic Agents Phase 2
20 Protective Agents Phase 2
21 Analgesics Phase 2
22 Hypolipidemic Agents Phase 1, Phase 2
23 Anticholesteremic Agents Phase 1, Phase 2
24 Lipid Regulating Agents Phase 1, Phase 2
25 Antimetabolites Phase 1, Phase 2
26 Antibodies, Monoclonal Phase 1, Phase 2
27 Antibodies Phase 1, Phase 2
28 Immunoglobulins Phase 1, Phase 2
29 Immunologic Factors Phase 1, Phase 2
30
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
31
Aspartic acid Approved, Nutraceutical 56-84-8 5960
32
Choline Approved, Nutraceutical 62-49-7 305
33 N-Methylaspartate

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 Botulinum Toxin in Patients With Hereditary Spastic Paraplegia: a Randomized, Double-blind, Placebo-controlled, Crossover Study Completed NCT02604186 Phase 2, Phase 3
2 Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5 Completed NCT02314208 Phase 2 Xenbilox;Tahor
3 Design and Validation of a Modular Physiotherapy Concept for the Treatment of Hereditary Spastic Spinal Paralysis (HSP) - a Randomized Study Completed NCT03961906 Phase 2
4 PCSK9 Inhibitor Treatment for Patients With Hereditary Spastic Paraplegia Type 5 Recruiting NCT04101643 Phase 1, Phase 2 evolocumab
5 Studying Cognition in SPG4 Compared to Healthy Controls Completed NCT03104088
6 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Completed NCT02852278
7 Nuclear Magnetic Spectroscopy for the Evaluation of Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
8 A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Completed NCT03627416
9 Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31 Recruiting NCT02859428
10 Studying the Presymptomatic and Early Phase of SPG4 Recruiting NCT03206190
11 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
12 Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood Recruiting NCT01568658
13 Improving Gait Adaptability in Hereditary Spastic Paraplegia During Task-specific Training on the C-Mill: Towards Evidence-Based and Individually Tailored Rehabilitation Recruiting NCT04180098
14 Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders Not yet recruiting NCT03981276

Search NIH Clinical Center for Spastic Paraplegia 3, Autosomal Dominant

Genetic Tests for Spastic Paraplegia 3, Autosomal Dominant

Genetic tests related to Spastic Paraplegia 3, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 3a, Autosomal Dominant 29

Anatomical Context for Spastic Paraplegia 3, Autosomal Dominant

MalaCards organs/tissues related to Spastic Paraplegia 3, Autosomal Dominant:

40
Tongue, Cortex, Spinal Cord, Eye, Bone, Kidney, Lung

Publications for Spastic Paraplegia 3, Autosomal Dominant

Articles related to Spastic Paraplegia 3, Autosomal Dominant:

(show top 50) (show all 133)
# Title Authors PMID Year
1
De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. 54 61 56 6
16533974 2006
2
Early onset autosomal dominant spastic paraplegia caused by novel mutations in SPG3A. 54 61 56 6
15517445 2004
3
Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. 54 61 56 6
11685207 2001
4
Late-onset hereditary spastic paraplegia with thin corpus callosum caused by a new SPG3A mutation. 61 56 6
21336785 2011
5
Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia. 61 56 6
12112092 2002
6
Do not trust the pedigree: reduced and sex-dependent penetrance at a novel mutation hotspot in ATL1 blurs autosomal dominant inheritance of spastic paraplegia. 56 6
23483706 2013
7
Infancy onset hereditary spastic paraplegia associated with a novel atlastin mutation. 56 6
12939451 2003
8
Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. 56 6
8252041 1993
9
X-linked hereditary spastic paraplegia. 56 6
4684346 1973
10
Characterization of a novel SPG3A deletion in a French-Canadian family. 54 61 6
17427918 2007
11
Atlastin1 mutations are frequent in young-onset autosomal dominant spastic paraplegia. 54 61 56
15596607 2004
12
SPG3A: An additional family carrying a new atlastin mutation. 54 61 6
12499504 2002
13
Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation. 61 56
24473461 2014
14
Spastic Paraplegia 3A 61 6
20862796 2010
15
Hereditary spastic paraplegia 3A associated with axonal neuropathy. 61 56
17502470 2007
16
A founder effect and mutational hot spots may contribute to the most frequent mutations in the SPG3A gene. 61 6
16612642 2006
17
SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. 61 56
16401858 2006
18
Incomplete penetrance in an SPG3A-linked family with a new mutation in the atlastin gene. 61 6
15184642 2004
19
Identification of a new form of autosomal dominant spastic paraplegia. 56
19519683 2009
20
The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity. 56
16894103 2006
21
Hereditary spastic paraplegia linked to chromosome 14q11-q21: reduction of the SPG3 locus interval from 5.3 to 2.7 cM. 56
11694553 2001
22
Hereditary Spastic Paraplegia Overview 6
20301682 2000
23
Genetic anticipation in a large family with pure autosomal dominant hereditary spastic paraplegia. 56
10232750 1999
24
Another pedigree with pure autosomal dominant spastic paraplegia (AD-FSP) from Tibet mapping to 14q11.2-q24.3. 56
9341882 1997
25
Advances in hereditary spastic paraplegia. 56
9266155 1997
26
Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait. 56
9042923 1997
27
Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. 56
8649538 1996
28
Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate region on chromosome 14q to 7 cM and locus heterogeneity. 56
7825576 1995
29
The phenotype of "pure" autosomal dominant spastic paraplegia. 56
8035929 1994
30
Sensory neuropathy in hereditary spastic paraplegia. 56
8006649 1994
31
Hereditary "pure" spastic paraplegia: a study of nine families. 56
8382269 1993
32
Central motor conduction studies in hereditary spastic paraplegia. 56
1659616 1991
33
Autosomal dominant familial spastic paraplegia: description of a large New England family and a study of management. 56
2286310 1990
34
A Dutch family with autosomal dominant pure spastic paraparesis (Strümpell's disease). 56
2270744 1990
35
Autosomal dominant familial spastic paraplegia: report of a large New England family. 56
2387086 1990
36
A quantitative study of sensory function in hereditary spastic paraplegia. 56
2364265 1990
37
The autosomal dominant form of "pure" familial spastic paraplegia: clinical findings and linkage analysis of a large pedigree. 56
3587641 1987
38
Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families. 56
7310405 1981
39
Slowly progressive autosomal dominant spastic paraplegia with late onset, variable expression and reduced penetrance: a basis for diagnosis and counseling. 56
7460376 1981
40
Hereditary spastic paraplegia with neurogenic bladder disturbances and syndactylia. 56
6249060 1980
41
Familial spastic paraplegia-clinical and pathologic studies in a large kindred. 56
703033 1978
42
Electrophysiological studies in familial spastic paraplegia. 56
903776 1977
43
Hereditary spastic paraplegia in Western Norway. 56
4426134 1974
44
Strümpell's familial spastic paraplegia: genetics and neuropathology. 56
4813430 1974
45
[Hereditary infantile spastic diplegia and its relation to familial spastic spinal paralysis]. 56
13517403 1957
46
Hereditary (familial) spastic paraplegia; further clinical and pathologic observations. 56
13282534 1956
47
[Genetic study of familial spasmodic paraplegia]. 56
12981238 1952
48
Hereditary spastic paraplegia with amyotrophy and pes cavus. 56
15415752 1950
49
Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia. 54 61
19423133 2009
50
Novel SPG3A and SPG4 mutations in two patients with Silver syndrome. 54 61
19730024 2009

Variations for Spastic Paraplegia 3, Autosomal Dominant

ClinVar genetic disease variations for Spastic Paraplegia 3, Autosomal Dominant:

6 (show top 50) (show all 73) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ATL1 NM_001127713.1(ATL1):c.596T>A (p.Leu199Gln)SNV Pathogenic 208489 rs797045004 14:51062316-51062316 14:50595598-50595598
2 ATL1 NM_001127713.1(ATL1):c.776C>A (p.Ser259Tyr)SNV Pathogenic 4347 rs119476047 14:51081143-51081143 14:50614425-50614425
3 ATL1 NM_001127713.1(ATL1):c.773A>G (p.His258Arg)SNV Pathogenic 4348 rs119476048 14:51081140-51081140 14:50614422-50614422
4 ATL1 ATL1, 1-BP INS, 1688Ainsertion Pathogenic 4350
5 ATL1 NM_001127713.1(ATL1):c.470T>G (p.Leu157Trp)SNV Pathogenic 4353 rs119476051 14:51058305-51058305 14:50591587-50591587
6 ATL1 NM_001127713.1(ATL1):c.1306_1308del (p.Asn436del)deletion Pathogenic 4354 14:51094935-51094937 14:50628217-50628219
7 ATL1 NM_001127713.1(ATL1):c.1519dupA (Ile507Asnfs)duplication Pathogenic 21528 rs863223314 14:51095146-51095147 14:50628428-50628429
8 ATL1 NM_001127713.1(ATL1):c.467C>T (p.Thr156Ile)SNV Pathogenic 21531 rs137852657 14:51058302-51058302 14:50591584-50591584
9 ATL1 NM_001127713.1(ATL1):c.1246C>T (p.Arg416Cys)SNV Pathogenic 30582 rs387906941 14:51094875-51094875 14:50628157-50628157
10 ATL1 NM_015915.5(ATL1):c.488T>C (p.Val163Ala)SNV Pathogenic 803025 14:51058323-51058323 14:50591605-50591605
11 ATL1 NM_015915.5(ATL1):c.1223T>C (p.Met408Thr)SNV Pathogenic 803026 14:51094852-51094852 14:50628134-50628134
12 ATL1 NM_001127713.1(ATL1):c.1160T>C (p.Leu387Ser)SNV Pathogenic/Likely pathogenic 659129 14:51094789-51094789 14:50628071-50628071
13 ATL1 NM_001127713.1(ATL1):c.715C>T (p.Arg239Cys)SNV Pathogenic/Likely pathogenic 4346 rs119476046 14:51080061-51080061 14:50613343-50613343
14 ATL1 NM_001127713.1(ATL1):c.1483C>T (p.Arg495Trp)SNV Pathogenic/Likely pathogenic 219827 rs864622269 14:51095112-51095112 14:50628394-50628394
15 ATL1 NM_001127713.1(ATL1):c.1243C>T (p.Arg415Trp)SNV Pathogenic/Likely pathogenic 4352 rs119476050 14:51094872-51094872 14:50628154-50628154
16 ATL1 NM_001127713.1(ATL1):c.757G>A (p.Val253Ile)SNV Pathogenic/Likely pathogenic 220424 rs864622520 14:51081124-51081124 14:50614406-50614406
17 ATL1 NM_001127713.1(ATL1):c.1193C>A (p.Ser398Tyr)SNV Likely pathogenic 219428 rs864622083 14:51094822-51094822 14:50628104-50628104
18 ATL1 NM_001127713.1(ATL1):c.650G>A (p.Arg217Gln)SNV Likely pathogenic 4349 rs119476049 14:51079996-51079996 14:50613278-50613278
19 ATL1 NM_001127713.1(ATL1):c.1222A>G (p.Met408Val)SNV Likely pathogenic 4351 rs28939094 14:51094851-51094851 14:50628133-50628133
20 ATL1 NM_001127713.1(ATL1):c.594A>C (p.Arg198Ser)SNV Likely pathogenic 471250 rs1555364247 14:51062314-51062314 14:50595596-50595596
21 ATL1 NM_015915.5(ATL1):c.1511del (p.Gly504fs)deletion Likely pathogenic 623150 rs1566735903 14:51095138-51095138 14:50628420-50628420
22 ATL1 NM_015915.5(ATL1):c.1217_1219AGA[1] (p.Lys407del)short repeat Likely pathogenic 807547 14:51094844-51094846 14:50628126-50628128
23 ATL1 NM_001127713.1(ATL1):c.1068T>A (p.Asn356Lys)SNV Likely pathogenic 640724 14:51089915-51089915 14:50623197-50623197
24 ATL1 NM_001127713.1(ATL1):c.1244G>A (p.Arg415Gln)SNV Likely pathogenic 56844 rs397514712 14:51094873-51094873 14:50628155-50628155
25 ATL1 NM_001127713.1(ATL1):c.536C>A (p.Ser179Tyr)SNV Likely pathogenic 538581 rs1555364149 14:51060577-51060577 14:50593859-50593859
26 ATL1 NM_001127713.1(ATL1):c.1024C>G (p.Pro342Ala)SNV Conflicting interpretations of pathogenicity 538579 rs1555365509 14:51088594-51088594 14:50621876-50621876
27 ATL1 NM_001127713.1(ATL1):c.478T>C (p.Ser160Pro)SNV Conflicting interpretations of pathogenicity 280749 rs886041897 14:51058313-51058313 14:50591595-50591595
28 ATL1 NM_001127713.1(ATL1):c.322A>G (p.Thr108Ala)SNV Uncertain significance 377500 rs112496709 14:51057698-51057698 14:50590980-50590980
29 ATL1 NM_001127713.1(ATL1):c.1078G>A (p.Val360Met)SNV Uncertain significance 390443 rs373267047 14:51089925-51089925 14:50623207-50623207
30 ATL1 NM_001127713.1(ATL1):c.461A>G (p.Gln154Arg)SNV Uncertain significance 410596 rs1060502971 14:51058296-51058296 14:50591578-50591578
31 ATL1 NM_001127713.1(ATL1):c.481G>T (p.Ala161Ser)SNV Uncertain significance 446866 rs1555363969 14:51058316-51058316 14:50591598-50591598
32 ATL1 NM_001127713.1(ATL1):c.311A>G (p.Asn104Ser)SNV Uncertain significance 450586 rs377736535 14:51057687-51057687 14:50590969-50590969
33 ATL1 NM_001127713.1(ATL1):c.1275A>G (p.Ile425Met)SNV Uncertain significance 471246 rs1273371448 14:51094904-51094904 14:50628186-50628186
34 ATL1 NM_001127713.1(ATL1):c.1057G>A (p.Glu353Lys)SNV Uncertain significance 471244 rs1555365595 14:51089904-51089904 14:50623186-50623186
35 ATL1 NM_001127713.1(ATL1):c.1213G>A (p.Val405Met)SNV Uncertain significance 471245 rs201240362 14:51094842-51094842 14:50628124-50628124
36 ATL1 NM_001127713.1(ATL1):c.1379T>A (p.Val460Glu)SNV Uncertain significance 471247 rs1555365871 14:51095008-51095008 14:50628290-50628290
37 ATL1 NM_001127713.1(ATL1):c.164G>A (p.Arg55Gln)SNV Uncertain significance 471248 rs564832738 14:51054678-51054678 14:50587960-50587960
38 ATL1 NM_001127713.1(ATL1):c.630+3G>ASNV Uncertain significance 471251 rs746263796 14:51062353-51062353 14:50595635-50595635
39 ATL1 NM_001127713.1(ATL1):c.874G>A (p.Glu292Lys)SNV Uncertain significance 471252 rs1360619786 14:51087328-51087328 14:50620610-50620610
40 ATL1 NM_001127713.1(ATL1):c.953A>T (p.Asn318Ile)SNV Uncertain significance 471253 rs770538531 14:51087407-51087407 14:50620689-50620689
41 ATL1 NM_001127713.1(ATL1):c.781_782insA (p.Phe261fs)insertion Uncertain significance 503888 rs1181733510 14:51081148-51081149 14:50614430-50614431
42 ATL1 NM_001127713.1(ATL1):c.769A>G (p.Ile257Val)SNV Uncertain significance 538577 rs1186954818 14:51081136-51081136 14:50614418-50614418
43 ATL1 NM_001127713.1(ATL1):c.46G>C (p.Glu16Gln)SNV Uncertain significance 538578 rs1223717112 14:51054560-51054560 14:50587842-50587842
44 ATL1 NM_001127713.1(ATL1):c.1041G>A (p.Met347Ile)SNV Uncertain significance 538583 rs1555365512 14:51088611-51088611 14:50621893-50621893
45 ATL1 NM_001127713.1(ATL1):c.1189G>C (p.Glu397Gln)SNV Uncertain significance 538576 rs148203226 14:51094818-51094818 14:50628100-50628100
46 ATL1 NM_001127713.1(ATL1):c.1551+1537G>ASNV Uncertain significance 538582 rs751861796 14:51096717-51096717 14:50629999-50629999
47 ATL1 NM_001127713.1(ATL1):c.300T>G (p.Val100=)SNV Uncertain significance 216696 rs863224772 14:51057676-51057676 14:50590958-50590958
48 ATL1 NM_001127713.1(ATL1):c.1206C>A (p.Phe402Leu)SNV Uncertain significance 560958 rs1566735714 14:51094835-51094835 14:50628117-50628117
49 ATL1 NM_001127713.1(ATL1):c.1222A>T (p.Met408Leu)SNV Uncertain significance 560959 rs28939094 14:51094851-51094851 14:50628133-50628133
50 ATL1 NM_001127713.1(ATL1):c.572A>G (p.Gln191Arg)SNV Uncertain significance 576063 rs1566725003 14:51060613-51060613 14:50593895-50593895

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 3, Autosomal Dominant:

73 (show all 17)
# Symbol AA change Variation ID SNP ID
1 ATL1 p.Arg217Gln VAR_017146 rs119476049
2 ATL1 p.Arg239Cys VAR_017147 rs119476046
3 ATL1 p.His258Arg VAR_017148 rs119476048
4 ATL1 p.Ser259Tyr VAR_017149 rs119476047
5 ATL1 p.Ala161Pro VAR_019446
6 ATL1 p.His247Pro VAR_019447
7 ATL1 p.Leu157Trp VAR_065509 rs119476051
8 ATL1 p.Met408Val VAR_065511 rs28939094
9 ATL1 p.Arg415Trp VAR_065512 rs119476050
10 ATL1 p.Gln154Glu VAR_067655
11 ATL1 p.Val253Ile VAR_067657 rs864622520
12 ATL1 p.Phe413Val VAR_067658
13 ATL1 p.Asn440Thr VAR_067659
14 ATL1 p.Arg495Trp VAR_067660 rs864622269
15 ATL1 p.Arg415Gln VAR_071708 rs397514712
16 ATL1 p.Arg416Cys VAR_071709 rs387906941
17 ATL1 p.Arg118Gln VAR_071874 rs606231265

Expression for Spastic Paraplegia 3, Autosomal Dominant

Search GEO for disease gene expression data for Spastic Paraplegia 3, Autosomal Dominant.

Pathways for Spastic Paraplegia 3, Autosomal Dominant

GO Terms for Spastic Paraplegia 3, Autosomal Dominant

Cellular components related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen-containing extracellular matrix GO:0062023 9.72 S100A4 POSTN FN1 CDH2 CCN2
2 cell-cell junction GO:0005911 9.67 TJP1 PECAM1 CDH5 CDH2
3 apical plasma membrane GO:0016324 9.65 TJP1 THY1 FN1 DDR2 CDH2
4 endoplasmic reticulum tubular network GO:0071782 9.4 REEP1 ATL1
5 catenin complex GO:0016342 9.33 CDH5 CDH2 CDH1
6 cell-cell adherens junction GO:0005913 9.26 TJP1 CDH5 CDH2 CDH1
7 adherens junction GO:0005912 8.92 TJP1 CDH5 CDH2 CDH1

Biological processes related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell migration GO:0030335 9.87 SNAI2 SNAI1 PECAM1 CDH5
2 cell migration GO:0016477 9.85 SNAI2 SNAI1 CDH2 CCN2
3 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007156 9.83 PECAM1 CDH5 CDH2 CDH1
4 angiogenesis GO:0001525 9.8 THY1 TBX1 PECAM1 FN1 CCN2
5 cell morphogenesis GO:0000902 9.77 CDH5 CDH2 CDH1
6 extracellular matrix organization GO:0030198 9.72 POSTN PECAM1 FN1 DDR2 CDH1
7 calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules GO:0016339 9.69 CDH5 CDH2 CDH1
8 adherens junction organization GO:0034332 9.67 CDH5 CDH2 CDH1
9 wound healing GO:0042060 9.67 SMAD2 POSTN PECAM1 FN1
10 cell-cell adhesion GO:0098609 9.65 THY1 PECAM1 CDH5 CDH2 CDH1
11 epithelial to mesenchymal transition GO:0001837 9.63 SNAI2 SNAI1 S100A4
12 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage GO:1902230 9.61 SNAI2 SNAI1
13 cell-cell adhesion mediated by cadherin GO:0044331 9.61 CDH5 CDH2 CDH1
14 negative regulation of DNA damage response, signal transduction by p53 class mediator GO:0043518 9.6 SNAI2 SNAI1
15 epithelial to mesenchymal transition involved in endocardial cushion formation GO:0003198 9.58 SNAI2 SNAI1
16 chondrocyte proliferation GO:0035988 9.58 DDR2 CCN2
17 Notch signaling involved in heart development GO:0061314 9.56 SNAI2 SNAI1
18 cartilage morphogenesis GO:0060536 9.54 SNAI2 SNAI1
19 negative regulation of vitamin D biosynthetic process GO:0010957 9.48 SNAI2 SNAI1
20 regulation of bicellular tight junction assembly GO:2000810 9.33 TJP1 SNAI2 SNAI1
21 cell adhesion GO:0007155 9.28 THY1 POSTN PECAM1 FN1 DDR2 CDH5
22 cell-cell junction assembly GO:0007043 9.26 TJP1 CDH5 CDH2 CDH1

Molecular functions related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cadherin binding GO:0045296 9.67 TJP1 CDH5 CDH2 CDH1
2 protein homodimerization activity GO:0042803 9.63 TBX1 SMAD2 PECAM1 CDH5 CDH2 CDH1
3 protein binding GO:0005515 9.62 TJP1 THY1 TBX1 SPG11 SPAST SNAI2
4 cytoskeletal protein binding GO:0008092 9.5 CDH5 CDH2 CDH1
5 gamma-catenin binding GO:0045295 9.26 CDH2 CDH1
6 beta-catenin binding GO:0008013 9.13 CDH5 CDH2 CDH1

Sources for Spastic Paraplegia 3, Autosomal Dominant

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