FSP
MCID: HRD010
MIFTS: 65

Hereditary Spastic Paraplegia (FSP)

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

Aliases & Classifications for Hereditary Spastic Paraplegia

MalaCards integrated aliases for Hereditary Spastic Paraplegia:

Name: Hereditary Spastic Paraplegia 12 73 25 20 53 58 36 29 6 15 37 32
Hereditary Spastic Paraparesis 12 25 20 58
Familial Spastic Paraplegia 12 20 58
Strumpell-Lorrain Disease 12 73 58
Spastic Paraplegia, Hereditary 44 70
Hsp 20 58
Spg 20 58
Spastic Paraplegia 3, Autosomal Dominant 70
Spastic Paraplegia Hereditary 54
Spastic Paraplegia, Familial 73
Familial Spastic Paraparesis 20
Strumpell-Lorrain Syndrome 25
French Settlement Disease 12
Strümpell-Lorrain Disease 20
Fsp 20

Characteristics:

Orphanet epidemiological data:

58
hereditary spastic paraplegia
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (Spain),1-9/100000 (Portugal),1-9/100000 (Worldwide),1-9/100000 (Tunisia),1-9/100000 (Norway),1-9/100000 (Italy),1-9/100000 (Estonia),1-9/100000 (Libyan Arab Jamahiriya); Age of onset: All ages;

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:2476
KEGG 36 H00266
ICD9CM 34 334.1
MeSH 44 D015419
NCIt 50 C140267
SNOMED-CT 67 267692008
ICD10 32 G11.4
ICD10 via Orphanet 33 G11.4
UMLS via Orphanet 71 C0037773 C2931355
Orphanet 58 ORPHA685
UMLS 70 C0037773 C2931355

Summaries for Hereditary Spastic Paraplegia

NINDS : 53 Hereditary spastic paraplegia (HSP), also called familial spastic paraparesis (FSP), refers to a group of inherited disorders that are characterized by progressive weakness and spasticity (stiffness) of the legs. Early in the disease course, there may be mild gait difficulties and stiffness. These symptoms typically slowly progress so that eventually individuals with HSP may require the assistance of a cane, walker, or wheelchair. Though the primary features of "pure" HSP are progressive lower limb spasticity and weakness, complicated forms may be accompanied by other symptoms. These additional symptoms include impaired vision due to cataracts and problems with the optic nerve and retina of the eye, ataxia (lack of muscle coordination), epilepsy, cognitive impairment, peripheral neuropathy, and deafness. The diagnosis of HSP is primarily by neurological examination and testing to rule out other disorders. Brain MRI abnormalities, such as a thin corpus callosum, may be seen in some of the complicated forms of HSP.  Several genetic mutations have been identified which underlie various forms of HSP, and specialized genetic testing and diagnosis are available at some medical centers.  HSP has several forms of inheritance.  Not all children in a family will necessarily develop symptoms, although they may be carriers of the abnormal gene.  Symptoms may begin in childhood or adulthood, depending on the particular HSP gene involved.

MalaCards based summary : Hereditary Spastic Paraplegia, also known as hereditary spastic paraparesis, is related to spastic paraplegia 2, x-linked and spastic paraplegia 15, autosomal recessive, and has symptoms including urgency of micturition, pain in lower limb and leg cramps. An important gene associated with Hereditary Spastic Paraplegia is KIF5A (Kinesin Family Member 5A), and among its related pathways/superpathways are Endocytosis and Lysosome. The drugs Acetylcholine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, eye and retina, and related phenotypes are spasticity and gait disturbance

Disease Ontology : 12 A paraplegia that is characterized by progressive stiffness and contraction (spasticity) in the lower limbs.

GARD : 20 Hereditary spastic paraplegia (HSP) is a group of hereditary, degenerative, neurological disorders that primarily affect the upper motor neurons. Upper motor neurons in the brain and spinal cord deliver signals to the lower motor neurons, which in turn, carry messages to the muscles. In hereditary spastic paraplegia, upper motor neurons slowly degenerate so the muscles do not receive the correct messages, causing progressive spasticity (increased muscle tone/stiffness) and weakness of the legs. This leads to difficulty walking. As degeneration continues, symptoms worsen. If only the lower body is affected, HSP is classified as uncomplicated or pure. HSP is classified as complicated or complex if other systems are involved. In these cases, additional symptoms, including impaired vision, ataxia, epilepsy, cognitive impairment, peripheral neuropathy, and/or deafness, occur. The different forms of HSP are caused by mutations in different genes. Inheritance varies. There are no specific treatments to prevent, slow, or reverse HSP. Individual symptoms may be treated with medications and/or physical therapy.

KEGG : 36 Hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive distal limb weakness and lower extremity spasticity.

Wikipedia : 73 Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive... more...

GeneReviews: NBK1509

Related Diseases for Hereditary Spastic Paraplegia

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 Dominant
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
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Spastic Paraplegia 83, Autosomal Recessive Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 30 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 Hereditary Spastic Paraplegia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 807)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 2, x-linked 34.1 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
2 spastic paraplegia 15, autosomal recessive 34.0 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
3 spastic paraplegia 4, autosomal dominant 33.9 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
4 masa syndrome 33.9 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
5 spastic paraplegia 10, autosomal dominant 33.9 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
6 spastic paraplegia 31, autosomal dominant 33.9 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
7 spastic paraplegia 6, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
8 spastic paraplegia 8, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
9 spastic paraplegia 39, autosomal recessive 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST GBA2
10 spastic paraplegia 18, autosomal recessive 33.8 ZFYVE26 WASHC5 SPG7 SPG11 REEP1 NIPA1
11 spastic paraplegia 3, autosomal dominant 33.8 WASHC5 SPG7 SPG11 SPAST REEP1 NIPA1
12 spastic paraplegia 12, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG11 SPAST REEP1 NIPA1
13 spastic paraplegia 20, autosomal recessive 33.8 ZFYVE26 SPG7 SPAST NIPA1 ATL1
14 spastic paraplegia 13, autosomal dominant 33.7 SPG7 SPG11 SPAST REEP1 NIPA1 KIF5A
15 spastic paraplegia 5a, autosomal recessive 33.7 ZFYVE26 SPG7 SPG11 SPAST KIF5A CYP7B1
16 hereditary spastic paraplegia 30 33.7 WASHC5 SPG7 SPG11 SPAST REEP1 KIF5A
17 paraplegia 33.7 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
18 spastic paraplegia 17, autosomal dominant 33.7 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
19 spastic paraplegia 48, autosomal recessive 33.7 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
20 spastic paraplegia 42, autosomal dominant 33.7 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
21 spastic paraplegia 35, autosomal recessive 33.6 ZFYVE26 WASHC5 SPG7 SPG11 REEP1 FA2H
22 spastic paraplegia 7, autosomal recessive 33.6 SPG7 SPG11
23 spastic paraplegia 46, autosomal recessive 33.6 ZFYVE26 SPG7 SPG11 SPAST GBA2 FA2H
24 spastic paraplegia 11, autosomal recessive 33.6 ZFYVE26 SPG7 SPG11 SPAST
25 spastic paraplegia 47, autosomal recessive 33.6 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
26 spastic paraplegia 26, autosomal recessive 33.6 SPG11 SPAST REEP1 GBA2 FA2H
27 hereditary spastic paraplegia 72 33.6 ZFYVE26 SPG7 SPG11 SPAST REEP1 ERLIN2
28 spastic paraplegia 56, autosomal recessive 33.6 ZFYVE26 SPG7 SPG11 SPAST GBA2 FA2H
29 spastic paraplegia 43, autosomal recessive 33.6 SPG11 SPAST GBA2 FA2H ERLIN2 C19orf12
30 spastic paraplegia 33, autosomal dominant 33.6 ZFYVE26 WASHC5 SPG11 SPAST REEP1 NIPA1
31 hereditary spastic paraplegia 23 33.5 ZFYVE26 WASHC5 SPG11 CYP7B1
32 spastic paraplegia 54, autosomal recessive 33.5 SPG7 SPG11 REEP1 GBA2 FA2H DDHD2
33 spastic paraplegia 57, autosomal recessive 33.5 SPG11 SACS REEP1 KIF5A KIF1A ERLIN2
34 spastic paraplegia 61, autosomal recessive 33.5 ZFYVE26 SPG11 SPAST REEP1 ATL1
35 spastic paraplegia 28, autosomal recessive 33.5 SPG7 SPG11 REEP1 FA2H DDHD2
36 spastic paraplegia 73, autosomal dominant 33.4 REEP1 GBA2 FA2H DDHD2 ATL1
37 spastic paraplegia 14, autosomal recessive 33.4 SPG7 SPG11 SPAST ATL1
38 spastic paraplegia 16, x-linked 33.4 WASHC5 SPG7 SPG11 SPAST
39 spastic paraplegia 49, autosomal recessive 33.4 ZFYVE26 SPG7 SPG11 DDHD2
40 spastic paraplegia 34, x-linked 33.4 ZFYVE26 WASHC5 REEP1
41 spastic paraplegia 32, autosomal recessive 33.4 WASHC5 SPG7 SPG11
42 spastic paraplegia 37, autosomal dominant 33.4 ZFYVE26 REEP1 ERLIN2
43 spastic paraplegia 25, autosomal recessive 33.3 ZFYVE26 WASHC5 REEP1
44 hereditary spastic paraplegia 51 33.3 ZFYVE26 SPG7 SPG11
45 spastic paraplegia 50, autosomal recessive 33.3 ZFYVE26 SPG7 SPG11
46 complex hereditary spastic paraplegia 33.3 SPG7 SPG11 SACS NIPA1 FA2H DDHD2
47 spastic paraplegia 44, autosomal recessive 33.3 SPG11 ERLIN2 CYP7B1
48 spastic paraplegia 63, autosomal recessive 33.3 SPG7 SPG11 CYP7B1
49 spastic paraplegia 55, autosomal recessive 33.3 ZFYVE26 SPG7 SPG11
50 pure hereditary spastic paraplegia 33.3 SPAST NIPA1 KIF5A ERLIN2 ATL1

Graphical network of the top 20 diseases related to Hereditary Spastic Paraplegia:



Diseases related to Hereditary Spastic Paraplegia

Symptoms & Phenotypes for Hereditary Spastic Paraplegia

Human phenotypes related to Hereditary Spastic Paraplegia:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 hallmark (90%) HP:0001257
2 gait disturbance 31 hallmark (90%) HP:0001288
3 impaired pain sensation 31 hallmark (90%) HP:0007328
4 paraplegia 31 hallmark (90%) HP:0010550
5 ataxia 31 frequent (33%) HP:0001251
6 finger syndactyly 31 occasional (7.5%) HP:0006101

UMLS symptoms related to Hereditary Spastic Paraplegia:


urgency of micturition; pain in lower limb; leg cramps

MGI Mouse Phenotypes related to Hereditary Spastic Paraplegia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.8 ATL1 CEP63 DDHD2 EPHB1 FA2H KIF1A
2 nervous system MP:0003631 9.44 CEP63 DDHD2 EPHB1 FA2H KIF1A KIF5A

Drugs & Therapeutics for Hereditary Spastic Paraplegia

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

(show all 37)
# 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 Cholinergic Agents Phase 2, Phase 3
4 Botulinum Toxins Phase 2, Phase 3
5
chenodeoxycholic acid Approved Phase 2 474-25-9 10133
6
Atorvastatin Approved Phase 2 134523-00-5 60823
7
Evolocumab Approved Phase 1, Phase 2 1256937-27-5
8
Miglustat Approved Phase 2 72599-27-0 51634
9
Resveratrol Investigational Phase 2 501-36-0 445154
10 Gastrointestinal Agents Phase 2
11 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 2
12 Analgesics, Non-Narcotic Phase 2
13 Protective Agents Phase 2
14 Cathartics Phase 2
15 Antirheumatic Agents Phase 2
16 Antioxidants Phase 2
17 Anti-Inflammatory Agents Phase 2
18 Analgesics Phase 2
19 Laxatives Phase 2
20 Platelet Aggregation Inhibitors Phase 2
21 Anti-Inflammatory Agents, Non-Steroidal Phase 2
22 Lipid Regulating Agents Phase 1, Phase 2
23 Anticholesteremic Agents Phase 1, Phase 2
24 Antimetabolites Phase 1, Phase 2
25 Hypolipidemic Agents Phase 1, Phase 2
26 Glycoside Hydrolase Inhibitors Phase 2
27 Anti-Retroviral Agents Phase 2
28 Antiviral Agents Phase 2
29 Anti-HIV Agents Phase 2
30 Anti-Infective Agents Phase 2
31 Cardiac Glycosides Phase 2
32 Hypoglycemic Agents Phase 2
33
Idebenone Approved, Investigational 58186-27-9
34
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
35
Choline Approved, Nutraceutical 62-49-7 305
36
Aspartic acid Approved, Nutraceutical 56-84-8 5960
37 N-Methylaspartate

Interventional clinical trials:

(show all 18)
# 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 Design and Validation of a Modular Physiotherapy Concept for the Treatment of Hereditary Spastic Spinal Paralysis (HSP) - a Randomized Study Completed NCT03961906 Phase 2
3 Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5 Completed NCT02314208 Phase 2 Xenbilox;Tahor
4 PCSK9 Inhibitor Treatment for Patients With Hereditary Spastic Paraplegia Type 5 Recruiting NCT04101643 Phase 1, Phase 2 evolocumab
5 Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11) Not yet recruiting NCT04768166 Phase 2 Miglustat
6 A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Completed NCT03627416
7 Nuclear Magnetic Spectroscopy for the Evaluation of Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
8 Studying Cognition in SPG4 Compared to Healthy Controls Completed NCT03104088
9 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Completed NCT02852278
10 Studying Non-motor Symptoms in Patients With Hereditary Spastic Paraplegia (HSP) Compared to Healthy Controls Completed NCT03204773
11 Improving Gait Adaptability in Hereditary Spastic Paraplegia During Task-specific Training on the C-Mill: Towards Evidence-Based and Individually Tailored Rehabilitation Recruiting NCT04180098
12 Registry and Natural History Study for AP-4 Associated Hereditary Spastic Paraplegia (AP-4-HSP) Recruiting NCT04712812
13 Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders Recruiting NCT03981276
14 Studying the Presymptomatic and Early Phase of SPG4 Recruiting NCT03206190
15 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
16 Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood Recruiting NCT01568658
17 SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP) Recruiting NCT04256681
18 Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31 Terminated NCT02859428

Search NIH Clinical Center for Hereditary Spastic Paraplegia

Cochrane evidence based reviews: spastic paraplegia, hereditary

Genetic Tests for Hereditary Spastic Paraplegia

Genetic tests related to Hereditary Spastic Paraplegia:

# Genetic test Affiliating Genes
1 Hereditary Spastic Paraplegia 29

Anatomical Context for Hereditary Spastic Paraplegia

MalaCards organs/tissues related to Hereditary Spastic Paraplegia:

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

Publications for Hereditary Spastic Paraplegia

Articles related to Hereditary Spastic Paraplegia:

(show top 50) (show all 1714)
# Title Authors PMID Year
1
Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. 61 25 6
9635427 1998
2
Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48. 25 6
24833714 2014
3
Functional evaluation of paraplegin mutations by a yeast complementation assay. 6 61 54
20186691 2010
4
Paraplegin mutations in sporadic adult-onset upper motor neuron syndromes. 6 25
18799786 2008
5
Hereditary spastic paraplegia caused by the novel mutation 1047insC in the SPG7 gene. 54 61 6
18563470 2008
6
Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia. 61 54 6
16534102 2006
7
FAHN/SPG35: a narrow phenotypic spectrum across disease classifications. 6 61
31135052 2019
8
Expanded phenotype in a patient with spastic paraplegia 7. 61 6
29026558 2017
9
Case series of autosomal recessive hereditary spastic paraparesis with novel mutation in SPG 7 gene. 61 6
29057857 2017
10
Progressive hereditary spastic paraplegia caused by a homozygous KY mutation. 6 61
28488683 2017
11
Clinical and genetic study of hereditary spastic paraplegia in Canada. 6 61
27957547 2017
12
Exome sequencing reveals two FA2H mutations in a family with a complicated form of Hereditary Spastic Paraplegia and psychiatric impairments. 6 61
28017243 2017
13
Genetic and phenotypic characterization of complex hereditary spastic paraplegia. 6 61
27217339 2016
14
A founder mutation p.H701P identified as a major cause of SPG7 in Norway. 61 6
26756429 2016
15
Autosomal recessive hereditary spastic paraplegia-clinical and genetic characteristics of a well-defined cohort. 6 61
23733235 2013
16
The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry. 6 61
23269439 2013
17
SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. 6 61
22571692 2013
18
Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy. 61 6
23065789 2012
19
Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. 61 6
21623769 2011
20
A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. 25 54 61
18200586 2008
21
Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia. 61 25 54
16489470 2006
22
De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. 54 61 25
16533974 2006
23
Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation. 54 61 25
15667412 2004
24
SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. 54 25 61
12134148 2002
25
KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia. 25 61
31488895 2020
26
A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia. 61 25
29528531 2018
27
ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree. 25 61
29453415 2018
28
Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia. 25 61
29524657 2018
29
Multigeneration family with dominant SPG30 hereditary spastic paraplegia. 25 61
29159194 2017
30
Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias. 6
28832565 2017
31
ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia. 61 25
28158749 2017
32
NT5C2 novel splicing variant expands the phenotypic spectrum of Spastic Paraplegia (SPG45): case report of a new member of thin corpus callosum SPG-Subgroup. 25 61
28327087 2017
33
ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia. 61 25
27738760 2017
34
Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia. 6
28362824 2017
35
Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. 61 25
26714052 2016
36
Hereditary and metabolic myelopathies. 25 61
27430441 2016
37
Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene. 25 61
26423925 2015
38
Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2. 61 25
26517984 2015
39
Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. 61 25
26026163 2015
40
Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. 25 61
25772097 2015
41
SPG7 mutations are a common cause of undiagnosed ataxia. 6
25681447 2015
42
Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. 61 25
25609768 2015
43
A complex form of hereditary spastic paraplegia in three siblings due to somatic mosaicism for a novel SPAST mutation in the mother. 61 25
25315759 2014
44
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. 61 25
25243380 2014
45
Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. 25 61
25008398 2014
46
Motor protein mutations cause a new form of hereditary spastic paraplegia. 61 25
24808017 2014
47
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. 61 25
24451228 2014
48
Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. 61 25
24388663 2014
49
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. 25 61
24319291 2014
50
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. 61 25
24355708 2014

Variations for Hereditary Spastic Paraplegia

ClinVar genetic disease variations for Hereditary Spastic Paraplegia:

6 (show top 50) (show all 125)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KIF26A NM_015656.1(KIF26A):c.1381del (p.Ala461fs) Deletion association 428591 rs1555389474 GRCh37: 14:104638963-104638963
GRCh38: 14:104172626-104172626
2 EPHB1 , CEP63 , KY NM_178554.6(KY):c.51_52insTATCGACATGTGCTGTATCTATCGACAT (p.Val18fs) Insertion Pathogenic 402246 rs1085307110 GRCh37: 3:134369751-134369752
GRCh38: 3:134650909-134650910
3 GBA2 NM_020944.3(GBA2):c.2618G>A (p.Arg873His) SNV Pathogenic 41490 rs398123015 GRCh37: 9:35737332-35737332
GRCh38: 9:35737335-35737335
4 CYP7B1 NM_004820.5(CYP7B1):c.914dup (p.Met305fs) Duplication Pathogenic 424649 rs1554524697 GRCh37: 8:65527725-65527726
GRCh38: 8:64615168-64615169
5 KIF5A NM_004984.4(KIF5A):c.839G>A (p.Arg280His) SNV Pathogenic 37130 rs387907288 GRCh37: 12:57963058-57963058
GRCh38: 12:57569275-57569275
6 GBA2 NM_020944.3(GBA2):c.1888C>T (p.Arg630Trp) SNV Pathogenic 41485 rs398123012 GRCh37: 9:35738808-35738808
GRCh38: 9:35738811-35738811
7 ZFYVE26 NM_015346.4(ZFYVE26):c.6296dup (p.Asn2100fs) Duplication Pathogenic 424650 rs1555394376 GRCh37: 14:68228992-68228993
GRCh38: 14:67762275-67762276
8 SPAST NM_014946.3(SPAST):c.1133T>A (p.Leu378Gln) SNV Pathogenic 424653 rs1553316816 GRCh37: 2:32352051-32352051
GRCh38: 2:32126982-32126982
9 KIF5A NM_004984.4(KIF5A):c.610C>T (p.Arg204Trp) SNV Pathogenic 424651 rs1555177629 GRCh37: 12:57961297-57961297
GRCh38: 12:57567514-57567514
10 SPG7 NM_003119.4(SPG7):c.376G>C (p.Glu126Gln) SNV Pathogenic 424654 rs912983346 GRCh37: 16:89579445-89579445
GRCh38: 16:89513037-89513037
11 SPG11 NM_025137.3(SPG11):c.(2244+1_2245-1)_(2620+1_2621-1)del Deletion Pathogenic 424655 GRCh37:
GRCh38:
12 SPG7 NM_003119.4(SPG7):c.771_772TG[1] (p.Val258fs) Microsatellite Pathogenic 504920 rs768136171 GRCh37: 16:89595899-89595900
GRCh38: 16:89529489-89529490
13 SPG11 NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs) Duplication Pathogenic 466523 rs750663981 GRCh37: 15:44891009-44891010
GRCh38: 15:44598811-44598812
14 SPG7 NM_003119.4(SPG7):c.1447C>T (p.Gln483Ter) SNV Pathogenic 390378 rs562890289 GRCh37: 16:89611178-89611178
GRCh38: 16:89544770-89544770
15 CYP7B1 NM_004820.5(CYP7B1):c.825T>A (p.Tyr275Ter) SNV Pathogenic 6105 rs121908613 GRCh37: 8:65528273-65528273
GRCh38: 8:64615716-64615716
16 SPG7 NM_003119.4(SPG7):c.1053dup (p.Gly352fs) Duplication Pathogenic 411675 rs760818649 GRCh37: 16:89598370-89598371
GRCh38: 16:89531962-89531963
17 KIF1A NM_004321.7(KIF1A):c.206C>T (p.Ser69Leu) SNV Pathogenic 188057 rs786200949 GRCh37: 2:241727625-241727625
GRCh38: 2:240788208-240788208
18 NIPA1 NM_144599.5(NIPA1):c.316G>A (p.Gly106Arg) SNV Pathogenic 2523 rs104894490 GRCh37: 15:23060816-23060816
GRCh38: 15:22812252-22812252
19 CYP7B1 NM_004820.5(CYP7B1):c.1456C>T (p.Arg486Cys) SNV Pathogenic 6107 rs116171274 GRCh37: 8:65509264-65509264
GRCh38: 8:64596707-64596707
20 KIF1A NM_004321.7(KIF1A):c.31C>T (p.Arg11Trp) SNV Pathogenic 424652 rs548204329 GRCh37: 2:241737139-241737139
GRCh38: 2:240797722-240797722
21 C19orf12 NM_001031726.3(C19orf12):c.157G>A (p.Gly53Arg) SNV Pathogenic 183298 rs200133991 GRCh37: 19:30199197-30199197
GRCh38: 19:29708290-29708290
22 SPG7 NM_003119.3(SPG7):c.1454_1462delGGCGGGAGA (p.Arg485_Glu487del) Deletion Pathogenic 411680 rs768823392 GRCh37: 16:89613065-89613073
GRCh38: 16:89546657-89546665
23 SPG11 NM_025137.4(SPG11):c.733_734del (p.Met245fs) Deletion Pathogenic 1112 rs312262720 GRCh37: 15:44949428-44949429
GRCh38: 15:44657230-44657231
24 SPG7 NM_003119.4(SPG7):c.1529C>T (p.Ala510Val) SNV Pathogenic/Likely pathogenic 42016 rs61755320 GRCh37: 16:89613145-89613145
GRCh38: 16:89546737-89546737
25 DDHD2 NM_015214.2(DDHD2):c.1249_1891del Deletion Likely pathogenic 183317 GRCh37:
GRCh38:
26 SH3TC2 NM_024577.3(SH3TC2):c.1402_1403delinsTT (p.Ala468Phe) Indel Likely pathogenic 216737 rs863224780 GRCh37: 5:148407892-148407893
GRCh38: 5:149028329-149028330
27 ERLIN2 NM_007175.8(ERLIN2):c.899A>T (p.Asp300Val) SNV Likely pathogenic 424656 rs763958615 GRCh37: 8:37611512-37611512
GRCh38: 8:37753994-37753994
28 KIF5A NM_004984.4(KIF5A):c.833C>T (p.Pro278Leu) SNV Likely pathogenic 424658 rs1555177824 GRCh37: 12:57963052-57963052
GRCh38: 12:57569269-57569269
29 REEP1 NM_001371279.1(REEP1):c.58G>C (p.Ala20Pro) SNV Likely pathogenic 424660 rs1266102026 GRCh37: 2:86509340-86509340
GRCh38: 2:86282217-86282217
30 SACS NM_014363.6(SACS):c.1640C>T (p.Pro547Leu) SNV Likely pathogenic 424657 rs140507581 GRCh37: 13:23929111-23929111
GRCh38: 13:23354972-23354972
31 KIF5A NM_004984.4(KIF5A):c.868G>C (p.Asp290His) SNV Likely pathogenic 424659 rs1555177831 GRCh37: 12:57963087-57963087
GRCh38: 12:57569304-57569304
32 PLEKHG5 NM_020631.6(PLEKHG5):c.773C>T (p.Pro258Leu) SNV Likely pathogenic 827645 rs910474236 GRCh37: 1:6533333-6533333
GRCh38: 1:6473273-6473273
33 FA2H NM_024306.5(FA2H):c.620C>T (p.Thr207Met) SNV Likely pathogenic 930104 GRCh37: 16:74753052-74753052
GRCh38: 16:74719154-74719154
34 USP8 NM_005154.5(USP8):c.254A>C (p.Tyr85Ser) SNV Uncertain significance 944583 GRCh37: 15:50741601-50741601
GRCh38: 15:50449404-50449404
35 USP8 NM_005154.5(USP8):c.886G>A (p.Val296Ile) SNV Uncertain significance 970553 GRCh37: 15:50769082-50769082
GRCh38: 15:50476885-50476885
36 USP8 NM_005154.5(USP8):c.823C>T (p.Arg275Trp) SNV Uncertain significance 528040 rs752682936 GRCh37: 15:50763966-50763966
GRCh38: 15:50471769-50471769
37 USP8 NM_005154.5(USP8):c.2443A>G (p.Asn815Asp) SNV Uncertain significance 528041 rs1555392171 GRCh37: 15:50785106-50785106
GRCh38: 15:50492909-50492909
38 USP8 NM_005154.5(USP8):c.397C>T (p.Arg133Trp) SNV Uncertain significance 528042 rs202135045 GRCh37: 15:50751258-50751258
GRCh38: 15:50459061-50459061
39 USP8 NM_005154.5(USP8):c.865G>A (p.Val289Ile) SNV Uncertain significance 570786 rs143070181 GRCh37: 15:50769061-50769061
GRCh38: 15:50476864-50476864
40 USP8 NM_005154.5(USP8):c.2320C>G (p.Pro774Ala) SNV Uncertain significance 577918 rs371064052 GRCh37: 15:50784983-50784983
GRCh38: 15:50492786-50492786
41 USP8 NC_000015.9:g.(?_50789266)_(50791305_?)dup Duplication Uncertain significance 584095 GRCh37: 15:50789266-50791305
GRCh38: 15:50497069-50499108
42 USP8 NM_005154.5(USP8):c.1460A>G (p.Gln487Arg) SNV Uncertain significance 644754 rs761395751 GRCh37: 15:50773919-50773919
GRCh38: 15:50481722-50481722
43 USP8 NM_005154.5(USP8):c.1531G>C (p.Glu511Gln) SNV Uncertain significance 652116 rs778969876 GRCh37: 15:50773990-50773990
GRCh38: 15:50481793-50481793
44 USP8 NM_005154.5(USP8):c.2246A>G (p.Tyr749Cys) SNV Uncertain significance 658247 rs898810598 GRCh37: 15:50784909-50784909
GRCh38: 15:50492712-50492712
45 ZFR NM_016107.5(ZFR):c.2072A>C (p.His691Pro) SNV Uncertain significance 694656 rs767783043 GRCh37: 5:32390451-32390451
GRCh38: 5:32390345-32390345
46 KIF1C NM_006612.6(KIF1C):c.2591G>A (p.Arg864His) SNV Uncertain significance 424676 rs146628704 GRCh37: 17:4925967-4925967
GRCh38: 17:5022672-5022672
47 AP5Z1 NM_014855.3(AP5Z1):c.272G>A (p.Arg91Gln) SNV Uncertain significance 424695 rs750211507 GRCh37: 7:4821291-4821291
GRCh38: 7:4781660-4781660
48 ARSI NM_001012301.4(ARSI):c.1456C>T (p.Arg486Cys) SNV Uncertain significance 424689 rs139095592 GRCh37: 5:149677031-149677031
GRCh38: 5:150297468-150297468
49 AP5Z1 NM_014855.3(AP5Z1):c.1111G>A (p.Ala371Thr) SNV Uncertain significance 424670 rs376671338 GRCh37: 7:4825294-4825294
GRCh38: 7:4785663-4785663
50 SLC16A2 NM_006517.5(SLC16A2):c.377C>A (p.Ser126Tyr) SNV Uncertain significance 424685 rs1555979601 GRCh37: X:73641849-73641849
GRCh38: X:74422014-74422014

Copy number variations for Hereditary Spastic Paraplegia from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 144964 2 32142183 32236210 Deletion SPAST hereditary spastic paraplegia

Expression for Hereditary Spastic Paraplegia

Search GEO for disease gene expression data for Hereditary Spastic Paraplegia.

Pathways for Hereditary Spastic Paraplegia

Pathways related to Hereditary Spastic Paraplegia according to KEGG:

36
# Name Kegg Source Accession
1 Endocytosis hsa04144
2 Lysosome hsa04142

GO Terms for Hereditary Spastic Paraplegia

Cellular components related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.21 ZFYVE26 WASHC5 SPG11 SPAST SACS REEP1
2 endoplasmic reticulum membrane GO:0005789 9.8 SPAST REEP1 GBA2 FA2H ERLIN2 CYP7B1
3 axon GO:0030424 9.72 SPG11 SACS KIF1A EPHB1 ATL1
4 endoplasmic reticulum tubular network GO:0071782 9.33 SPAST REEP1 ATL1
5 endoplasmic reticulum GO:0005783 9.32 WASHC5 SPAST REEP1 GBA2 FA2H ERLIN2
6 axon cytoplasm GO:1904115 9.26 SPG7 SPAST KIF5A KIF1A

Biological processes related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.65 GBA2 FA2H ERLIN2 DDHD2 CYP7B1
2 steroid metabolic process GO:0008202 9.58 GBA2 ERLIN2 CYP7B1
3 cytoskeleton-dependent intracellular transport GO:0030705 9.37 KIF5A KIF1A
4 cholesterol metabolic process GO:0008203 9.33 GBA2 ERLIN2 CYP7B1
5 synaptic vesicle transport GO:0048489 9.32 SPG11 KIF5A
6 retrograde neuronal dense core vesicle transport GO:1990049 8.96 KIF5A KIF1A
7 anterograde axonal transport GO:0008089 8.8 SPG7 SPAST KIF1A

Molecular functions related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule binding GO:0008017 9.26 SPAST REEP1 KIF5A KIF1A
2 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 9.16 KIF5A KIF1A
3 ATPase activity GO:0016887 8.92 SPG7 SPAST KIF5A KIF1A

Sources for Hereditary Spastic Paraplegia

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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