FSP
MCID: HRD010
MIFTS: 66

Hereditary Spastic Paraplegia (FSP)

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 Hereditary Spastic Paraplegia

MalaCards integrated aliases for Hereditary Spastic Paraplegia:

Name: Hereditary Spastic Paraplegia 12 74 24 52 53 58 36 29 6 15 37 32
Hereditary Spastic Paraparesis 12 24 52 58
Familial Spastic Paraplegia 12 52 58
Strumpell-Lorrain Disease 12 74 58
Spastic Paraplegia, Hereditary 43 71
Hsp 52 58
Spg 52 58
Spastic Paraplegia 3, Autosomal Dominant 71
Spastic Paraplegia Hereditary 54
Spastic Paraplegia, Familial 74
Familial Spastic Paraparesis 52
Strumpell-Lorrain Syndrome 24
French Settlement Disease 12
Strümpell-Lorrain Disease 52
Fsp 52

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 43 D015419
SNOMED-CT 67 39912006 76043009
ICD10 32 G11.4
ICD10 via Orphanet 33 G11.4
UMLS via Orphanet 72 C0037773 C2931355
Orphanet 58 ORPHA685
UMLS 71 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 hereditary spastic paraplegia 72 and hereditary spastic paraplegia 23, and has symptoms including urgency of micturition, pain in lower limb and leg cramps. An important gene associated with Hereditary Spastic Paraplegia is SPAST (Spastin), 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 brain, spinal cord and bone, 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.

NIH Rare Diseases : 52 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 : 74 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 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 Hereditary Spastic Paraplegia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 717)
# Related Disease Score Top Affiliating Genes
1 hereditary spastic paraplegia 72 35.8 ZFYVE26 SPG11 SPAST REEP1 NIPA1 ATL1
2 hereditary spastic paraplegia 23 35.7 ZFYVE26 WASHC5 SPG11 SPART CYP7B1
3 spastic paraplegia 4, autosomal dominant 35.6 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
4 spastic paraplegia 31, autosomal dominant 35.6 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
5 spastic paraplegia 2, x-linked 35.6 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
6 masa syndrome 35.6 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
7 spastic paraplegia 20, autosomal recessive 35.5 ZFYVE26 SPG7 SPG11 SPAST SPART NIPA1
8 hereditary spastic paraplegia 51 35.5 ZFYVE26 SPG11 NIPA1 AP5Z1
9 spastic paraplegia 15, autosomal recessive 35.4 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
10 spastic paraplegia 17, autosomal dominant 35.4 ZFYVE26 WASHC5 SPG11 SPAST SPART REEP1
11 pure hereditary spastic paraplegia 35.4 SPAST NIPA1 KIF5A ATL1
12 complex hereditary spastic paraplegia 35.4 SPG7 SPG11 NIPA1 CYP7B1
13 spastic paraplegia 10, autosomal dominant 35.4 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
14 spastic paraplegia 6, autosomal dominant 35.3 ZFYVE27 ZFYVE26 WASHC5 SPG11 SPAST SPART
15 spastic paraplegia 8, autosomal dominant 35.3 ZFYVE27 ZFYVE26 WASHC5 SPG11 SPAST SPART
16 spastic paraplegia 3, autosomal dominant 35.3 ZFYVE26 WASHC5 SPG11 SPAST REEP1 NIPA1
17 spastic paraplegia 42, autosomal dominant 35.3 ZFYVE27 ZFYVE26 WASHC5 SPG11 SPAST SPART
18 spastic paraplegia 30, autosomal recessive 35.2 WASHC5 SPG11 SPAST REEP1 NIPA1 KIF5A
19 spastic paraplegia 12, autosomal dominant 35.2 ZFYVE27 ZFYVE26 WASHC5 SPG11 SPAST REEP1
20 spastic paraplegia 18, autosomal recessive 35.2 ZFYVE26 WASHC5 SPG7 SPG11 REEP1 NIPA1
21 spastic paraplegia 5a, autosomal recessive 35.2 ZFYVE26 SPG7 SPG11 SPAST KIF5A CYP7B1
22 spastic paraplegia 13, autosomal dominant 35.2 SPG7 SPAST REEP1 NIPA1 KIF5A HSPD1
23 spastic paraplegia 39, autosomal recessive 35.2 ZFYVE26 WASHC5 SPG11 SPAST SPART GBA2
24 spastic paraplegia 48, autosomal recessive 35.2 ZFYVE26 WASHC5 SPG11 SPAST REEP1 ATL1
25 spastic paraplegia 35, autosomal recessive 35.1 ZFYVE26 WASHC5 SPG7 SPG11 REEP1 C19orf12
26 spastic paraplegia 26, autosomal recessive 35.1 ZFYVE26 WASHC5 SPG11 SPAST SPART REEP1
27 spastic paraplegia 43, autosomal recessive 35.1 ZFYVE27 ZFYVE26 SPG11 SPAST GBA2 C19orf12
28 spastic paraplegia 11, autosomal recessive 35.0 ZFYVE26 SPG7 SPG11
29 spastic paraplegia 54, autosomal recessive 35.0 SPG7 SPG11 REEP1 GBA2 AP5Z1
30 spastic paraplegia 46, autosomal recessive 35.0 ZFYVE26 SPG7 SPG11 GBA2 AP5Z1
31 spastic paraplegia 57, autosomal recessive 35.0 SPG11 REEP1 KIF5A KIF1A ALS2
32 spastic paraplegia 14, autosomal recessive 35.0 ZFYVE26 WASHC5 SPG11 SPAST
33 spastic paraplegia 16, x-linked 35.0 ZFYVE26 WASHC5 SPG11 SPAST
34 spastic paraplegia 28, autosomal recessive 35.0 SPG7 SPG11 REEP1 CYP7B1
35 spastic paraplegia 33, autosomal dominant 34.9 ZFYVE27 WASHC5 SPAST SPART REEP1 NIPA1
36 spastic paraplegia 77, autosomal recessive 34.9 ZFYVE26 SPG11 GBA2 CYP7B1
37 spastic paraplegia 44, autosomal recessive 34.9 ZFYVE27 ZFYVE26 WASHC5 AP5Z1
38 spastic paraplegia 7, autosomal recessive 34.9 SPG7 AFG3L2
39 spastic paraplegia 32, autosomal recessive 34.9 ZFYVE26 SPG7 SPG11
40 spastic paraplegia 61, autosomal recessive 34.9 SPAST REEP1 ATL1
41 spastic paraplegia 56, autosomal recessive 34.9 SPG11 GBA2 AP5Z1
42 spastic paraplegia 64, autosomal recessive 34.9 SPG7 SPG11 ALS2
43 mast syndrome 34.8 ZFYVE27 SPG11 SPART
44 spastic paraplegia 47, autosomal recessive 34.8 ZFYVE26 WASHC5 SPG11 REEP1 AP5Z1
45 spastic paraplegia 50, autosomal recessive 34.8 ZFYVE26 WASHC5 SPG11 NIPA1 AP5Z1
46 spastic paraplegia 34, x-linked 34.8 ZFYVE26 WASHC5
47 spastic paraplegia 29, autosomal dominant 34.8 ZFYVE26 WASHC5
48 spastic paraplegia 37, autosomal dominant 34.8 ZFYVE26 WASHC5
49 spastic paraplegia 19, autosomal dominant 34.7 ZFYVE26 WASHC5
50 spastic paraplegia 25, autosomal recessive 34.7 ZFYVE26 WASHC5

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:

58 31 (show all 6)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
2 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
3 impaired pain sensation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007328
4 paraplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0010550
5 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
6 finger syndactyly 58 31 occasional (7.5%) Occasional (29-5%) 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:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.77 AFG3L2 ALS2 ATL1 HSPD1 KIF1A KIF5A
2 nervous system MP:0003631 9.4 AFG3L2 ALS2 HSPD1 KIF1A KIF5A KY

Drugs & Therapeutics for Hereditary Spastic Paraplegia

Drugs for Hereditary Spastic Paraplegia (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 16)
# 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 Nuclear Magnetic Spectroscopy for the Evaluation of Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
6 A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Completed NCT03627416
7 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Completed NCT02852278
8 Studying Cognition in SPG4 Compared to Healthy Controls Completed NCT03104088
9 Improving Gait Adaptability in Hereditary Spastic Paraplegia During Task-specific Training on the C-Mill: Towards Evidence-Based and Individually Tailored Rehabilitation Recruiting NCT04180098
10 Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31 Recruiting NCT02859428
11 Studying the Presymptomatic and Early Phase of SPG4 Recruiting NCT03206190
12 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
13 Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood Recruiting NCT01568658
14 Studying Non-motor Symptoms in Patients With Hereditary Spastic Paraplegia (HSP) Compared to Healthy Controls Recruiting NCT03204773
15 Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders Not yet recruiting NCT03981276
16 Investigating the Role of SPG20,STK31 Genes in the Carcinogenesis of Colorectal Cancer Not yet recruiting NCT03261752

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
Brain, Spinal Cord, Bone, Eye, Testes, Retina, Kidney

Publications for Hereditary Spastic Paraplegia

Articles related to Hereditary Spastic Paraplegia:

(show top 50) (show all 1556)
# Title Authors PMID Year
1
A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. 54 61 24
18200586 2008
2
Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia. 54 61 24
16489470 2006
3
De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. 54 61 24
16533974 2006
4
Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation. 54 61 24
15667412 2004
5
SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. 54 61 24
12134148 2002
6
A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia. 61 24
29528531 2018
7
Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia. 61 24
29524657 2018
8
ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree. 61 24
29453415 2018
9
ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia. 61 24
28158749 2017
10
NT5C2 novel splicing variant expands the phenotypic spectrum of Spastic Paraplegia (SPG45): case report of a new member of thin corpus callosum SPG-Subgroup. 61 24
28327087 2017
11
ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia. 61 24
27738760 2017
12
Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. 61 24
26714052 2016
13
Hereditary and metabolic myelopathies. 61 24
27430441 2016
14
Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene. 61 24
26423925 2015
15
Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2. 61 24
26517984 2015
16
Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. 61 24
26026163 2015
17
Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. 61 24
25772097 2015
18
Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. 61 24
25609768 2015
19
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. 61 24
25243380 2014
20
A complex form of hereditary spastic paraplegia in three siblings due to somatic mosaicism for a novel SPAST mutation in the mother. 61 24
25315759 2014
21
Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. 61 24
25008398 2014
22
Motor protein mutations cause a new form of hereditary spastic paraplegia. 61 24
24808017 2014
23
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. 61 24
24451228 2014
24
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. 61 24
24319291 2014
25
Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. 61 24
24388663 2014
26
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. 61 24
24355708 2014
27
Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis. 61 24
24103911 2013
28
Recurrent de novo c.316G>A mutation in NIPA1 hotspot. 61 24
24075313 2013
29
Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. 61 24
23857908 2013
30
Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. 61 24
23746551 2013
31
Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. 61 24
23664120 2013
32
Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. 61 24
23176824 2012
33
Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. 61 24
23176821 2012
34
Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia. 61 24
23176823 2012
35
Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) . 61 24
22290197 2012
36
Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. 61 24
22232211 2012
37
A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18). 61 24
21796390 2011
38
NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy. 61 24
21599812 2011
39
Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1. 61 24
21419568 2011
40
Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism. 61 24
21381113 2011
41
Hereditary spastic paraplegia-like disorder due to a mitochondrial ATP6 gene point mutation. 61 24
20656066 2011
42
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. 61 24
20613862 2010
43
Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). 61 24
20104589 2010
44
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. 61 24
19652142 2009
45
CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. 61 24
19439420 2009
46
New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia (HSP). 61 24
19034539 2009
47
Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. 61 24
19056803 2009
48
Forceps minor region signal abnormality "ears of the lynx": an early MRI finding in spastic paraparesis with thin corpus callosum and mutations in the spatacsin gene (SPG11) on chromosome 15. 61 24
19040626 2009
49
SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. 61 24
18337587 2008
50
Hereditary spastic paraplegia 3A associated with axonal neuropathy. 61 24
17502470 2007

Variations for Hereditary Spastic Paraplegia

ClinVar genetic disease variations for Hereditary Spastic Paraplegia:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SPG11 NM_025137.4(SPG11):c.733_734del (p.Met245fs)deletion Pathogenic 1112 rs312262720 15:44949428-44949429 15:44657230-44657231
2 NIPA1 NM_144599.5(NIPA1):c.316G>A (p.Gly106Arg)SNV Pathogenic 2523 rs104894490 15:23060816-23060816 15:22812252-22812252
3 CYP7B1 NM_004820.5(CYP7B1):c.825T>A (p.Tyr275Ter)SNV Pathogenic 6105 rs121908613 8:65528273-65528273 8:64615716-64615716
4 KY NM_178554.6(KY):c.51_52insTATCGACATGTGCTGTATCTATCGACAT (p.Val18fs)insertion Pathogenic 402246 rs1085307110 3:134369751-134369752 3:134650909-134650910
5 SPG7 NM_003119.4(SPG7):c.1053dup (p.Gly352fs)duplication Pathogenic 411675 rs760818649 16:89598370-89598371 16:89531962-89531963
6 SPAST NM_014946.3(SPAST):c.1133T>A (p.Leu378Gln)SNV Pathogenic 424653 rs1553316816 2:32352051-32352051 2:32126982-32126982
7 CYP7B1 NM_004820.5(CYP7B1):c.914dup (p.Met305fs)duplication Pathogenic 424649 rs1554524697 8:65527725-65527726 8:64615168-64615169
8 KIF5A NM_004984.4(KIF5A):c.610C>T (p.Arg204Trp)SNV Pathogenic 424651 rs1555177629 12:57961297-57961297 12:57567514-57567514
9 ZFYVE26 NM_015346.4(ZFYVE26):c.6296dup (p.Asn2100fs)duplication Pathogenic 424650 rs1555394376 14:68228992-68228993 14:67762275-67762276
10 SPG11 NM_025137.3(SPG11):c.(2244+1_2245-1)_(2620+1_2621-1)deldeletion Pathogenic 424655
11 SPG11 NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs)duplication Pathogenic 466523 rs750663981 15:44891009-44891010 15:44598811-44598812
12 SPG7 NM_003119.4(SPG7):c.771_772TG[1] (p.Val258fs)short repeat Pathogenic 504920 rs768136171 16:89595899-89595900 16:89529489-89529490
13 SPG7 NM_003119.4(SPG7):c.376G>C (p.Glu126Gln)SNV Pathogenic/Likely pathogenic 424654 rs912983346 16:89579445-89579445 16:89513037-89513037
14 SPG7 NM_003119.4(SPG7):c.1447C>T (p.Gln483Ter)SNV Pathogenic/Likely pathogenic 390378 rs562890289 16:89611178-89611178 16:89544770-89544770
15 SPG7 NM_003119.3(SPG7):c.1454_1462delGGCGGGAGA (p.Arg485_Glu487del)deletion Pathogenic/Likely pathogenic 411680 rs768823392 16:89613065-89613073 16:89546657-89546665
16 C19orf12 NM_001256047.1(C19orf12):c.124G>A (p.Gly42Arg)SNV Pathogenic/Likely pathogenic 183298 rs200133991 19:30199197-30199197 19:29708290-29708290
17 KIF1A NM_004321.7(KIF1A):c.206C>T (p.Ser69Leu)SNV Pathogenic/Likely pathogenic 188057 rs786200949 2:241727625-241727625 2:240788208-240788208
18 GBA2 NM_020944.3(GBA2):c.1888C>T (p.Arg630Trp)SNV Pathogenic/Likely pathogenic 41485 rs398123012 9:35738808-35738808 9:35738811-35738811
19 GBA2 NM_020944.3(GBA2):c.2618G>A (p.Arg873His)SNV Pathogenic/Likely pathogenic 41490 rs398123015 9:35737332-35737332 9:35737335-35737335
20 DDHD2 NM_015214.2(DDHD2):c.1249_1891deldeletion Likely pathogenic 183317
21 REEP1 NM_001164731.2(REEP1):c.25-18176G>CSNV Likely pathogenic 424660 rs1266102026 2:86509340-86509340 2:86282217-86282217
22 KIF5A NM_004984.4(KIF5A):c.833C>T (p.Pro278Leu)SNV Likely pathogenic 424658 rs1555177824 12:57963052-57963052 12:57569269-57569269
23 KIF5A NM_004984.4(KIF5A):c.868G>C (p.Asp290His)SNV Likely pathogenic 424659 rs1555177831 12:57963087-57963087 12:57569304-57569304
24 ERLIN2 NM_007175.8(ERLIN2):c.899A>T (p.Asp300Val)SNV Likely pathogenic 424656 rs763958615 8:37611512-37611512 8:37753994-37753994
25 KIF1C NM_006612.6(KIF1C):c.1111G>A (p.Ala371Thr)SNV Conflicting interpretations of pathogenicity 424675 rs142056835 17:4908241-4908241 17:5004946-5004946
26 KIF1C NM_006612.6(KIF1C):c.2299G>A (p.Gly767Arg)SNV Conflicting interpretations of pathogenicity 424674 rs118037269 17:4925675-4925675 17:5022380-5022380
27 SACS NM_014363.6(SACS):c.5629C>T (p.Arg1877Ter)SNV Conflicting interpretations of pathogenicity 371545 rs761089024 13:23912386-23912386 13:23338247-23338247
28 KIF1A NM_004321.7(KIF1A):c.31C>T (p.Arg11Trp)SNV Conflicting interpretations of pathogenicity 424652 rs548204329 2:241737139-241737139 2:240797722-240797722
29 SETX NM_015046.7(SETX):c.3826C>G (p.Gln1276Glu)SNV Conflicting interpretations of pathogenicity 424692 rs148604312 9:135203159-135203159 9:132327772-132327772
30 SETX NM_015046.7(SETX):c.3229G>A (p.Asp1077Asn)SNV Conflicting interpretations of pathogenicity 424687 rs145097270 9:135203756-135203756 9:132328369-132328369
31 MAG NM_002361.4(MAG):c.452C>T (p.Ala151Val)SNV Conflicting interpretations of pathogenicity 424686 rs144553163 19:35790493-35790493 19:35299590-35299590
32 SPG7 NM_003119.4(SPG7):c.1529C>T (p.Ala510Val)SNV Conflicting interpretations of pathogenicity 42016 rs61755320 16:89613145-89613145 16:89546737-89546737
33 SPG11 NM_025137.4(SPG11):c.3818A>G (p.Lys1273Arg)SNV Conflicting interpretations of pathogenicity 130365 rs76389165 15:44890903-44890903 15:44598705-44598705
34 BICD2 NM_001003800.2(BICD2):c.269A>G (p.Lys90Arg)SNV Conflicting interpretations of pathogenicity 235235 rs61754130 9:95491490-95491490 9:92729208-92729208
35 SACS NM_014363.6(SACS):c.1373C>T (p.Thr458Ile)SNV Conflicting interpretations of pathogenicity 282385 rs61729954 13:23929378-23929378 13:23355239-23355239
36 ALS2 NM_020919.4(ALS2):c.3206G>A (p.Gly1069Glu)SNV Conflicting interpretations of pathogenicity 333592 rs200706696 2:202591249-202591249 2:201726526-201726526
37 NIPA1 NM_144599.5(NIPA1):c.24_26GGC[10] (p.Ala15_Ala16dup)short repeat Conflicting interpretations of pathogenicity 193496 rs531550505 15:23086364-23086365 15:22786677-22786678
38 SACS NM_014363.6(SACS):c.13717A>C (p.Asn4573His)SNV Conflicting interpretations of pathogenicity 193707 rs34382952 13:23904298-23904298 13:23330159-23330159
39 KIF1C NM_006612.6(KIF1C):c.2734C>T (p.Arg912Trp)SNV Conflicting interpretations of pathogenicity 209167 rs202232792 17:4926868-4926868 17:5023573-5023573
40 CYP7B1 NM_004820.5(CYP7B1):c.1456C>T (p.Arg486Cys)SNV Conflicting interpretations of pathogenicity 6107 rs116171274 8:65509264-65509264 8:64596707-64596707
41 KIF5A NM_004984.4(KIF5A):c.839G>A (p.Arg280His)SNV Conflicting interpretations of pathogenicity 37130 rs387907288 12:57963058-57963058 12:57569275-57569275
42 SPG7 NM_003119.4(SPG7):c.1933T>A (p.Ser645Thr)SNV Uncertain significance 215194 rs2099104 16:89619540-89619540 16:89553132-89553132
43 SACS NM_014363.6(SACS):c.1640C>T (p.Pro547Leu)SNV Uncertain significance 311560 rs140507581 13:23929111-23929111 13:23354972-23354972
44 WDR48 NM_020839.4(WDR48):c.280T>G (p.Ser94Ala)SNV Uncertain significance 424665 rs148407227 3:39108050-39108050 3:39066559-39066559
45 CCT5 NM_012073.5(CCT5):c.487G>A (p.Glu163Lys)SNV Uncertain significance 424664 rs552008894 5:10256222-10256222 5:10256110-10256110
46 ARSI NM_001012301.4(ARSI):c.1456C>T (p.Arg486Cys)SNV Uncertain significance 424689 rs139095592 5:149677031-149677031 5:150297468-150297468
47 ARSI NM_001012301.4(ARSI):c.1114G>A (p.Asp372Asn)SNV Uncertain significance 424672 rs150211860 5:149677373-149677373 5:150297810-150297810
48 AP4M1 NM_004722.4(AP4M1):c.607-2A>GSNV Uncertain significance 424662 rs755533568 7:99702495-99702495 7:100104872-100104872
49 AP5Z1 NM_014855.3(AP5Z1):c.272G>A (p.Arg91Gln)SNV Uncertain significance 424695 rs750211507 7:4821291-4821291 7:4781660-4781660
50 AP5Z1 NM_014855.3(AP5Z1):c.838A>C (p.Thr280Pro)SNV Uncertain significance 424671 rs554060393 7:4824586-4824586 7:4784955-4784955

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

Pathways related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.32 ZFYVE27 WASHC5 SPART KIF5A

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 endoplasmic reticulum membrane GO:0005789 9.88 ZFYVE27 SPAST REEP1 GBA2 CYP7B1 ATL1
2 endoplasmic reticulum GO:0005783 9.86 ZFYVE27 WASHC5 SPAST REEP1 GBA2 CYP7B1
3 axon GO:0030424 9.72 ZFYVE27 SPG11 KIF1A ATL1 ALS2
4 early endosome GO:0005769 9.67 WASHC5 NIPA1 HSPD1 ALS2
5 m-AAA complex GO:0005745 9.16 SPG7 AFG3L2
6 endoplasmic reticulum tubular network GO:0071782 9.13 ZFYVE27 REEP1 ATL1
7 axon cytoplasm GO:1904115 8.92 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 endosomal transport GO:0016197 9.43 WASHC5 AP5Z1 ALS2
2 mitochondrial calcium ion transmembrane transport GO:0006851 9.4 SPG7 AFG3L2
3 synaptic vesicle transport GO:0048489 9.37 SPG11 KIF5A
4 mitochondrial calcium ion homeostasis GO:0051560 9.32 C19orf12 AFG3L2
5 retrograde neuronal dense core vesicle transport GO:1990049 9.16 KIF5A KIF1A
6 anterograde axonal transport GO:0008089 9.13 SPG7 SPAST KIF1A
7 axonogenesis GO:0007409 8.92 SPAST ATL1 ALS2 AFG3L2

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

# Name GO ID Score Top Affiliating Genes
1 unfolded protein binding GO:0051082 9.33 SPG7 HSPD1 AFG3L2
2 microtubule binding GO:0008017 9.26 SPAST REEP1 KIF5A KIF1A
3 ATPase activity GO:0016887 8.92 SPAST KIF5A KIF1A HSPD1

Sources for Hereditary Spastic Paraplegia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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