Details of Disease

General Information of Disease (ID: DISGZQV1)

Disease Name Hereditary spastic paraplegia
Synonyms
familial spastic paraparesis; FSP; spastic paraplegia; familial spastic paraplegia; Strmpell-Lorrain disease; SPG; hereditary spastic paraparesis; HSP; Strumpell-Lorrain disease; French settlement disease
Definition
Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs.
Disease Hierarchy
DISSKWBI: Paraplegia
DISLG2RO: Hereditary neuromuscular disease
DISPN7D2: Inherited neurodegenerative disorder
DISGZQV1: Hereditary spastic paraplegia
Disease Identifiers
MONDO ID
MONDO_0019064
MESH ID
D015419
UMLS CUI
C0037773
MedGen ID
20844
Orphanet ID
685
SNOMED CT ID
39912006

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 68 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
ZFR OTYDAOT8 Limited Autosomal recessive [1]
AFG3L2 OTRPMAUX Limited Genetic Variation [21]
ALDH18A1 OT6W40XU Limited Biomarker [22]
CPT1C OT8F1MBF Limited Autosomal dominant [23]
DNM2 OTUYU2U3 Limited Autosomal dominant [1]
ERLIN2 OT551BVG Limited Genetic Variation [24]
GPT2 OTS5VF7N Limited Genetic Variation [25]
HSPA14 OTZCA5LK Limited Genetic Variation [26]
IMMT OTBDSLE7 Limited Genetic Variation [27]
KIF5B OTT34MT8 Limited Genetic Variation [28]
KIF5C OT35570Y Limited Genetic Variation [28]
NOP56 OTT67SRZ Limited Genetic Variation [29]
PCBP1 OTHN0TD7 Limited Genetic Variation [30]
REEP2 OTPCRA5O Limited Biomarker [31]
SPG11 OTZ7LJX4 Limited Biomarker [32]
SPG7 OT8OY9ST Limited Genetic Variation [21]
TECPR2 OT1UFECZ Limited Biomarker [33]
AP4B1 OTGJUIRA moderate Genetic Variation [34]
ATP13A2 OTKWBUGK moderate Genetic Variation [35]
DDHD2 OTUP0WHF moderate Genetic Variation [36]
GBA2 OTOZXG5D moderate Genetic Variation [37]
AAAS OTJT9T23 Strong Biomarker [38]
ABCD1 OT3FL9W0 Strong X-linked [15]
ALS2 OT8BAM04 Strong Genetic Variation [39]
AP4E1 OT4DUNVU Strong Biomarker [40]
AP4M1 OT2BG2Z3 Strong Biomarker [40]
ATAD3A OTWF6HBP Strong Genetic Variation [41]
ATL1 OTR2788Y Strong Genetic Variation [42]
ATXN7 OTL3YF1H Strong Genetic Variation [4]
B4GALNT1 OTCY80HS Strong Genetic Variation [43]
BICD2 OTVJ03NZ Strong Genetic Variation [44]
BSCL2 OT73V6Y4 Strong Biomarker [45]
C19orf12 OTVSJ1AR Strong Biomarker [46]
CDSN OTQW4HV6 Strong Genetic Variation [47]
DCTN1 OT5B51FJ Strong Biomarker [48]
DPY30 OTLHCJ6C Strong Genetic Variation [49]
DSTYK OTUL75IR Strong Genetic Variation [50]
DYNC1H1 OTD1KRKO Strong Genetic Variation [48]
ERLIN1 OTUOOODY Strong Genetic Variation [24]
FA2H OT8HA13U Strong Biomarker [51]
FAR1 OTLHTYIE Strong Biomarker [52]
IBA57 OT9SPG2X Strong Genetic Variation [47]
IFT122 OTSK3OAD Strong Genetic Variation [53]
KIF1A OT3JVEGV Strong Genetic Variation [54]
KIF1B OTI1XQTO Strong Biomarker [55]
KIF1C OTKYLP1Q Strong Genetic Variation [56]
KY OTK1L8VX Strong CausalMutation [6]
LY6E OTMG16BZ Strong Genetic Variation [4]
MAD2L1BP OT2O2IUJ Strong Biomarker [55]
NIPA1 OT9ODC8X Strong Genetic Variation [57]
PLA2G6 OT5FL0WU Strong Genetic Variation [58]
PLP1 OT8CM9CX Strong Genetic Variation [59]
POLR3A OT5MSK10 Strong Genetic Variation [60]
REEP1 OTEMVFX7 Strong Biomarker [61]
RNASEH2B OT8KHYFY Strong Biomarker [62]
RNF170 OT2O6F4D Strong Genetic Variation [24]
RTN1 OTCX1SMK Strong Biomarker [63]
RTN2 OTTZ5FW0 Strong Biomarker [64]
SELENOI OTX2A47A Strong Genetic Variation [65]
SPART OTIVOS2I Strong Genetic Variation [66]
SPG21 OTMKJSYS Strong Genetic Variation [34]
TFG OT2KJENI Strong Genetic Variation [67]
AP4S1 OTM3QBU8 Definitive Biomarker [40]
AP5Z1 OTXIPLFH Definitive Autosomal recessive [23]
ARL6IP1 OT536XAV Definitive Autosomal recessive [23]
CYP2U1 OT6RXLXS Definitive Autosomal recessive [23]
DDHD1 OTWTHOWK Definitive Autosomal recessive [23]
PQBP1 OTXCBEAH Definitive Biomarker [68]
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⏷ Show the Full List of 68 DOT(s)
This Disease Is Related to 14 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
DNM2 TTVRA5G Limited Autosomal dominant [1]
HSPD1 TT9HL5R moderate Genetic Variation [2]
ATP1A1 TTWK8D0 Strong Genetic Variation [3]
ATXN3 TT6A17J Strong Genetic Variation [4]
CAPN1 TT1WBIJ Strong Genetic Variation [5]
EPHB1 TT8MDAC Strong CausalMutation [6]
GJC2 TTPOCAL Strong Genetic Variation [7]
HSPE1 TTWYMFE Strong Genetic Variation [8]
KCNA2 TTVFB0O Strong Genetic Variation [9]
L1CAM TTC9D3K Strong Genetic Variation [10]
MAG TT9XFON Strong Genetic Variation [11]
PNPLA6 TTWAQU2 Strong Genetic Variation [12]
ST3GAL5 TTVF2BJ Strong Genetic Variation [13]
VCP TTHNLSB Strong Genetic Variation [14]
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⏷ Show the Full List of 14 DTT(s)
This Disease Is Related to 2 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
ABCD1 DTKM9DZ Strong X-linked [15]
ABCD1 DTKM9DZ Strong Genetic Variation [16]
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This Disease Is Related to 4 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
CYP7B1 DE36TMY Limited CausalMutation [17]
CYP39A1 DEEG96X Strong Genetic Variation [18]
FXN DEXVHDB Strong Genetic Variation [19]
PCYT2 DEIX1PO Strong Biomarker [20]
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References

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2 MitCHAP-60 and Hereditary Spastic Paraplegia SPG-13 Arise from an Inactive hsp60 Chaperonin that Fails to Fold the ATP Synthase -Subunit.Sci Rep. 2019 Aug 23;9(1):12300. doi: 10.1038/s41598-019-48762-5.
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9 A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.Ann Neurol. 2016 Oct;80(4):638-42. doi: 10.1002/ana.24762. Epub 2016 Sep 9.
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17 Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias.Eur J Hum Genet. 2017 Nov;25(11):1217-1228. doi: 10.1038/ejhg.2017.124. Epub 2017 Aug 23.
18 Liver disease in infancy caused by oxysterol 7 -hydroxylase deficiency: successful treatment with chenodeoxycholic acid.J Inherit Metab Dis. 2014 Sep;37(5):851-61. doi: 10.1007/s10545-014-9695-6.
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20 Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain. 2019 Nov 1;142(11):3382-3397. doi: 10.1093/brain/awz291.
21 m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.Cell Res. 2018 Mar;28(3):296-306. doi: 10.1038/cr.2018.17. Epub 2018 Feb 16.
22 P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9.Ann Clin Transl Neurol. 2019 Aug;6(8):1533-1540. doi: 10.1002/acn3.50821. Epub 2019 Jul 19.
23 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
24 Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.Nat Commun. 2019 Oct 21;10(1):4790. doi: 10.1038/s41467-019-12620-9.
25 GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.Clin Genet. 2018 Oct;94(3-4):356-361. doi: 10.1111/cge.13390. Epub 2018 Jul 10.
26 The Hsp60-(p.V98I) mutation associated with hereditary spastic paraplegia SPG13 compromises chaperonin function both in vitro and in vivo.J Biol Chem. 2008 Jun 6;283(23):15694-700. doi: 10.1074/jbc.M800548200. Epub 2008 Apr 8.
27 Theoretical Investigations of the Role of Mutations in Dynamics of Kinesin Motor Proteins.J Phys Chem B. 2018 May 3;122(17):4653-4661. doi: 10.1021/acs.jpcb.8b00830. Epub 2018 Apr 23.
28 SPG10 is a rare cause of spastic paraplegia in European families.J Neurol Neurosurg Psychiatry. 2008 May;79(5):584-7. doi: 10.1136/jnnp.2007.137596. Epub 2008 Feb 1.
29 Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.Clin Genet. 2016 Aug;90(2):141-8. doi: 10.1111/cge.12706. Epub 2016 Jan 20.
30 Mutant HSPB1 causes loss of translational repression by binding to PCBP1, an RNA binding protein with a possible role in neurodegenerative disease.Acta Neuropathol Commun. 2017 Jan 11;5(1):5. doi: 10.1186/s40478-016-0407-3.
31 Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting.Rev Neurol (Paris). 2015 Jun-Jul;171(6-7):505-30. doi: 10.1016/j.neurol.2015.02.017. Epub 2015 May 23.
32 Human SPG11 cerebral organoids reveal cortical neurogenesis impairment.Hum Mol Genet. 2019 Mar 15;28(6):961-971. doi: 10.1093/hmg/ddy397.
33 WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.Clin Genet. 2016 Aug;90(2):182-5. doi: 10.1111/cge.12730. Epub 2016 Feb 10.
34 Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.J Neurol Sci. 2012 Jul 15;318(1-2):1-18. doi: 10.1016/j.jns.2012.03.025. Epub 2012 May 1.
35 The Parkinson-associated human P5B-ATPase ATP13A2 modifies lipid homeostasis.Biochim Biophys Acta Biomembr. 2019 Oct 1;1861(10):182993. doi: 10.1016/j.bbamem.2019.05.015. Epub 2019 May 24.
36 Defining the clinical-genetic and neuroradiological features in SPG54: description of eight additional cases and nine novel DDHD2 variants.J Neurol. 2019 Nov;266(11):2657-2664. doi: 10.1007/s00415-019-09466-y. Epub 2019 Jul 13.
37 Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.J Biol Chem. 2019 Mar 15;294(11):3853-3871. doi: 10.1074/jbc.RA118.006311. Epub 2019 Jan 20.
38 The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.PLoS Genet. 2016 Dec 2;12(12):e1006463. doi: 10.1371/journal.pgen.1006463. eCollection 2016 Dec.
39 A novel homozygous mutation in ALS2 gene in four siblings with infantile-onset ascending hereditary spastic paralysis.Eur J Med Genet. 2014 May-Jun;57(6):275-8. doi: 10.1016/j.ejmg.2014.03.006. Epub 2014 Apr 3.
40 Generation and characterization of six human induced pluripotent stem cell lines (iPSC) from three families with AP4B1-associated hereditary spastic paraplegia (SPG47).Stem Cell Res. 2019 Oct;40:101575. doi: 10.1016/j.scr.2019.101575. Epub 2019 Sep 11.
41 ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia.Hum Mol Genet. 2017 Apr 15;26(8):1432-1443. doi: 10.1093/hmg/ddx042.
42 Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites.Nat Commun. 2019 Feb 4;10(1):568. doi: 10.1038/s41467-019-08478-6.
43 Loss of Enzyme Activity in Mutated B4GALNT1 Gene Products in Patients with Hereditary Spastic Paraplegia Results in Relatively Mild Neurological Disorders: Similarity with Phenotypes of B4galnt1 Knockout Mice.Neuroscience. 2019 Jan 15;397:94-106. doi: 10.1016/j.neuroscience.2018.11.034. Epub 2018 Dec 4.
44 BICD2 mutational analysis in hereditary spastic paraplegia and hereditary motor and sensory neuropathy.Muscle Nerve. 2019 Apr;59(4):484-486. doi: 10.1002/mus.26394. Epub 2018 Dec 21.
45 ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia.J Neurol. 2017 Jan;264(1):11-20. doi: 10.1007/s00415-016-8301-2. Epub 2016 Oct 13.
46 Clinical and genetic spectrum of an orphan disease MPAN: a series with new variants and a novel phenotype.Neurol Neurochir Pol. 2019;53(6):476-483. doi: 10.5603/PJNNS.a2019.0062. Epub 2019 Dec 5.
47 Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015 Feb 17;84(7):659-67. doi: 10.1212/WNL.0000000000001270. Epub 2015 Jan 21.
48 Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies.Clin Genet. 2016 Aug;90(2):127-33. doi: 10.1111/cge.12712. Epub 2016 Feb 16.
49 Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.Brain. 2018 May 1;141(5):1286-1299. doi: 10.1093/brain/awy034.
50 A locus for complicated hereditary spastic paraplegia maps to chromosome 1q24-q32.Ann Neurol. 2003 Dec;54(6):796-803. doi: 10.1002/ana.10768.
51 Autosomal recessive hereditary spastic paraplegia type SPG35 due to a novel variant in the FA2H gene in a Czech patient.J Clin Neurosci. 2019 Jan;59:337-339. doi: 10.1016/j.jocn.2018.10.094. Epub 2018 Nov 13.
52 Going Too Far Is the Same as Falling Short(?: Kinesin-3 Family Members in Hereditary Spastic Paraplegia.Front Cell Neurosci. 2019 Sep 26;13:419. doi: 10.3389/fncel.2019.00419. eCollection 2019.
53 Genetic analysis of SPG4 and SPG3A genes in a cohort of Chinese patients with hereditary spastic paraplegia.J Neurol Sci. 2014 Dec 15;347(1-2):368-71. doi: 10.1016/j.jns.2014.10.017. Epub 2014 Oct 16.
54 Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors.Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18429-18434. doi: 10.1073/pnas.1905690116. Epub 2019 Aug 27.
55 A network biology approach to unraveling inherited axonopathies.Sci Rep. 2019 Feb 8;9(1):1692. doi: 10.1038/s41598-018-37119-z.
56 Clinical phenotype of hereditary spastic paraplegia due to KIF1C gene mutations across life span.Brain Dev. 2018 Jun;40(6):458-464. doi: 10.1016/j.braindev.2018.02.013. Epub 2018 Mar 12.
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58 PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia.J Hum Genet. 2019 Jan;64(1):55-59. doi: 10.1038/s10038-018-0519-7. Epub 2018 Oct 9.
59 Teriflunomide attenuates neuroinflammation-related neural damage in mice carrying human PLP1 mutations.J Neuroinflammation. 2018 Jul 3;15(1):194. doi: 10.1186/s12974-018-1228-z.
60 Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.Brain. 2017 Jun 1;140(6):1561-1578. doi: 10.1093/brain/awx095.
61 Peripheral neuropathy in hereditary spastic paraplegia caused by REEP1 variants.J Neurol. 2019 Mar;266(3):735-744. doi: 10.1007/s00415-019-09196-1. Epub 2019 Jan 12.
62 RNASEH2B Pathogenic Gene Variant in Uncomplicated Hereditary Spastic Paraplegia: Report of a New Patient.Neuropediatrics. 2018 Dec;49(6):419. doi: 10.1055/s-0038-1672174. Epub 2018 Sep 17.
63 Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein.Neurogenetics. 2006 May;7(2):93-103. doi: 10.1007/s10048-006-0034-4. Epub 2006 Apr 7.
64 Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. J Clin Invest. 2012 Feb;122(2):538-44. doi: 10.1172/JCI60560. Epub 2012 Jan 9.
65 A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis.Brain. 2017 Mar 1;140(3):547-554. doi: 10.1093/brain/aww318.
66 Three cases of Troyer syndrome in two families of Filipino descent.Am J Med Genet A. 2016 Jul;170(7):1780-5. doi: 10.1002/ajmg.a.37658. Epub 2016 Apr 26.
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