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Gene Review

SPG7  -  spastic paraplegia 7 (pure and complicated...

Homo sapiens

Synonyms: CAR, CMAR, PGN, Paraplegin, SPG5C, ...
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Disease relevance of SPG7


High impact information on SPG7


Chemical compound and disease context of SPG7


Biological context of SPG7

  • A significant decrease in mitochondrial respiratory chain complexes I and IV was demonstrated in the non-SPG4/SPG7 group [2].
  • Four different SPG7 mutations have been described so far in association with both pure and complicated HSP phenotypes [10].
  • Muscle biopsies from two SPG7 mutation patients did not show any histological evidence of an oxidative phosphorylation defect [10].
  • The 17 exons and flanking regions of the SPG7 gene were screened for mutations using a combination of single-stranded conformation polymorphism (SSCP) analysis and sequencing [10].
  • Dissipation of membrane potential, expression of m-AAA protease paraplegin, or induction of apoptosis stimulated this processing along with the mitochondrial fragmentation [11].

Anatomical context of SPG7

  • We show that adenoassociated virus-mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice [4].
  • Here, we analyze the assembly of paraplegin into m-AAA complexes and monitor consequences of paraplegin deficiency in HSP fibroblasts and in a mouse model for HSP [12].
  • They suggest, rather, that the activity of cell wall may be caused by a sCD14-binding molecule that associates noncovalently with PGN [13].
  • Distinct phagocyte subsets, including granulocytes, macrophages, and dendritic cells, contained PGN in the brain and coexpressed the inflammatory cytokine interleukin-12 [14].
  • Therefore, mammalian PGRP binds to PGN and Gram-positive bacteria with nanomolar affinity, is expressed in neutrophils, and inhibits growth of bacteria [15].

Associations of SPG7 with chemical compounds

  • The ability of G908R, R702W, and L1007fsinsC variants in the presence and absence of P268S to confer responsiveness to lipopolysaccharide (LPS) and peptidoglycan (PGN) was determined in HEK293T kidney cells [16].
  • NOD2 recognizes muramyl dipeptide (MDP) derived from bacterial peptidoglycan (PGN), but the molecular basis of recognition remains elusive [17].
  • Our results indicate that Gram-positive bacterial is a biologically relevant ligand for MBL, and that the collectin preferentially binds to the GlcNAc moiety of the PGN via its C-type lectin domains [8].
  • We report that human PGRP-L is a Zn2+-dependent N-acetylmuramoyl-l-alanine amidase (EC, an enzyme that hydrolyzes the amide bond between MurNAc and l-Ala of bacterial PGN [18].
  • The minimum PGN fragment hydrolyzed by PGRP-L is MurNAc-tripeptide [18].

Other interactions of SPG7

  • We therefore conclude that there is evidence for mitochondrial dysfunction in non-SPG4/SPG7 HSP [2].
  • Finally, analysis of a muscle biopsy specimen from one patient was normal, suggesting that, contrary to SPG7, mitochondrial disturbance could not be a primary feature of SPG9 [19].
  • Two genes have been identified: paraplegin and sacsin [20].
  • Identification and characterization of AFG3L2, a novel paraplegin-related gene [21].
  • Identification and characterization of YME1L1, a novel paraplegin-related gene [22].

Analytical, diagnostic and therapeutic context of SPG7


  1. Genomic structure and expression analysis of the spastic paraplegia gene, SPG7. Settasatian, C., Whitmore, S.A., Crawford, J., Bilton, R.L., Cleton-Jansen, A.M., Sutherland, G.R., Callen, D.F. Hum. Genet. (1999) [Pubmed]
  2. Investigation of mitochondrial function in hereditary spastic paraparesis. McDermott, C.J., Taylor, R.W., Hayes, C., Johnson, M., Bushby, K.M., Turnbull, D.M., Shaw, P.J. Neuroreport (2003) [Pubmed]
  3. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Dürr, A., Fontaine, B., Ballabio, A. Cell (1998) [Pubmed]
  4. Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia. Pirozzi, M., Quattrini, A., Andolfi, G., Dina, G., Malaguti, M.C., Auricchio, A., Rugarli, E.I. J. Clin. Invest. (2006) [Pubmed]
  5. Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England. McDermott, C.J., Dayaratne, R.K., Tomkins, J., Lusher, M.E., Lindsey, J.C., Johnson, M.A., Casari, G., Turnbull, D.M., Bushby, K., Shaw, P.J. Neurology (2001) [Pubmed]
  6. Structural basis for peptidoglycan binding by peptidoglycan recognition proteins. Guan, R., Roychowdhury, A., Ember, B., Kumar, S., Boons, G.J., Mariuzza, R.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. Toll-like receptor 2 and 4 (TLR2 and TLR4) agonists differentially regulate secretory interleukin-1 receptor antagonist gene expression in macrophages. Carl, V.S., Brown-Steinke, K., Nicklin, M.J., Smith, M.F. J. Biol. Chem. (2002) [Pubmed]
  8. Mannose-binding lectin recognizes peptidoglycan via the N-acetyl glucosamine moiety, and inhibits ligand-induced proinflammatory effect and promotes chemokine production by macrophages. Nadesalingam, J., Dodds, A.W., Reid, K.B., Palaniyar, N. J. Immunol. (2005) [Pubmed]
  9. Binding of bacterial peptidoglycan to CD14. Dziarski, R., Tapping, R.I., Tobias, P.S. J. Biol. Chem. (1998) [Pubmed]
  10. A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia. Wilkinson, P.A., Crosby, A.H., Turner, C., Bradley, L.J., Ginsberg, L., Wood, N.W., Schapira, A.H., Warner, T.T. Brain (2004) [Pubmed]
  11. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. Ishihara, N., Fujita, Y., Oka, T., Mihara, K. EMBO J. (2006) [Pubmed]
  12. Variable and Tissue-Specific Subunit Composition of Mitochondrial m-AAA Protease Complexes Linked to Hereditary Spastic Paraplegia. Koppen, M., Metodiev, M.D., Casari, G., Rugarli, E.I., Langer, T. Mol. Cell. Biol. (2007) [Pubmed]
  13. Chemical characteristics of Staphylococcus aureus molecules that have CD14-dependent cell-stimulating activity. Kusunoki, T., Wright, S.D. J. Immunol. (1996) [Pubmed]
  14. Phagocytes Containing a Disease-Promoting Toll-Like Receptor/Nod Ligand Are Present in the Brain during Demyelinating Disease in Primates. Visser, L., Melief, M.J., van Riel, D., van Meurs, M., Sick, E.A., Inamura, S., Bajramovic, J.J., Amor, S., Hintzen, R.Q., Boven, L.A., 't Hart, B.A., Laman, J.D. Am. J. Pathol. (2006) [Pubmed]
  15. Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. Liu, C., Gelius, E., Liu, G., Steiner, H., Dziarski, R. J. Biol. Chem. (2000) [Pubmed]
  16. Crohn's disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan. Bonen, D.K., Ogura, Y., Nicolae, D.L., Inohara, N., Saab, L., Tanabe, T., Chen, F.F., Foster, S.J., Duerr, R.H., Brant, S.R., Cho, J.H., Nuñez, G. Gastroenterology (2003) [Pubmed]
  17. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. Tanabe, T., Chamaillard, M., Ogura, Y., Zhu, L., Qiu, S., Masumoto, J., Ghosh, P., Moran, A., Predergast, M.M., Tromp, G., Williams, C.J., Inohara, N., Núñez, G. EMBO J. (2004) [Pubmed]
  18. Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. Wang, Z.M., Li, X., Cocklin, R.R., Wang, M., Wang, M., Fukase, K., Inamura, S., Kusumoto, S., Gupta, D., Dziarski, R. J. Biol. Chem. (2003) [Pubmed]
  19. A refined physical and transcriptional map of the SPG9 locus on 10q23.3-q24.2. Lo Nigro, C., Cusano, R., Scaranari, M., Cinti, R., Forabosco, P., Morra, V.B., De Michele, G., Santoro, L., Davies, S., Hurst, J., Devoto, M., Ravazzolo, R., Seri, M. Eur. J. Hum. Genet. (2000) [Pubmed]
  20. Recent advances in hereditary spastic paraplegia. Tallaksen, C.M., Dürr, A., Brice, A. Curr. Opin. Neurol. (2001) [Pubmed]
  21. Identification and characterization of AFG3L2, a novel paraplegin-related gene. Banfi, S., Bassi, M.T., Andolfi, G., Marchitiello, A., Zanotta, S., Ballabio, A., Casari, G., Franco, B. Genomics (1999) [Pubmed]
  22. Identification and characterization of YME1L1, a novel paraplegin-related gene. Coppola, M., Pizzigoni, A., Banfi, S., Bassi, M.T., Casari, G., Incerti, B. Genomics (2000) [Pubmed]
  23. Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia. Elleuch, N., Depienne, C., Benomar, A., Hernandez, A.M., Ferrer, X., Fontaine, B., Grid, D., Tallaksen, C.M., Zemmouri, R., Stevanin, G., Durr, A., Brice, A. Neurology (2006) [Pubmed]
  24. Modulation of connexin expression and gap junction communication in astrocytes by the gram-positive bacterium S. aureus. Esen, N., Shuffield, D., Syed, M.M., Kielian, T. Glia (2007) [Pubmed]
  25. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Suzuki, K., Honda, K., Tanabe, K., Toma, H., Nihei, H., Yamaguchi, Y. Kidney Int. (2003) [Pubmed]
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