SPG20

Spastic paraplegia 20 (Troyer syndrome)
PDB rendering based on 2dl1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2DL1​, 4U7I​
Identifiers
Symbols	SPG20 ; SPARTIN; TAHCCP1
External IDs	OMIM: 607111 MGI: 2139806 HomoloGene: 32243 GeneCards: SPG20 Gene
Gene ontology Molecular function • protein binding • ubiquitin protein ligase binding Cellular component • cytoplasm • mitochondrial outer membrane • lipid particle • plasma membrane • midbody • synapse Biological process • abscission • negative regulation of BMP signaling pathway • lipid particle organization • negative regulation of collateral sprouting in absence of injury • neuromuscular process • cell division • regulation of mitochondrial membrane potential • adipose tissue development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23111	229285
Ensembl	ENSG00000133104	ENSMUSG00000036580
UniProt	Q8N0X7	Q8R1X6
RefSeq (mRNA)	NM_001142294	NM_001144987
RefSeq (protein)	NP_001135766	NP_001138459
Location (UCSC)	Chr 13: 36.3 – 36.37 Mb	Chr 3: 55.11 – 55.14 Mb
PubMed search

Spartin is a protein that in humans is encoded by the SPG20 gene.^[1][2][3]

This gene encodes a protein that contains a MIT (Microtubule Interacting and Trafficking molecule) domain. This protein may be involved in endosomal trafficking, microtubule dynamics, or both functions. Frameshift mutations associated with this gene cause autosomal recessive spastic paraplegia 20 (Troyer syndrome).^[3]

Troyer syndrome (SPG20) is a complicated type of hereditary spastic paraplegias (HSPs).^[4] HSP is a category of neurological disorder characterized by spasticity and muscle weakness in the lower limbs.^[4]

Background

The original description of this gene mutation and associated symptoms were described in 1967.^[5] This mutation is commonly found in high frequency with the Amish population.^[2] Newer studies have found that the mutation is not isolated to the Amish population, but also resides in the Omani population.^[5]

Presentation

This syndrome is not only characterized by spasticity and weakness in the lower limbs, but also with dysarthria, mental retardation or mild developmental delay, and muscle wasting or muscle atrophy.^[4]

Physical

Individuals appear to have difficulty walking, and report a clumsy, spastic gait which worsens over time.^[5] Some additional common physical features include overgrowth of the jaw bone, hammer toes, hand and feet abnormalities, and pes cavus.^[5]

Cognitive

Cognitive challenges, including developmental delay and difficulty with performance in school, may affect individuals with this syndrome.^[5]

Neurologic

Neurologic examination of individuals with this mutation may show dysmetria in the upper extremities, hyperreflexia, distal amyotrophy and ankle clonus, in addition to spasticity, weakness and dysarthria.^[5]

Diagnostic Imaging

The cerebellar vermis may present with mild atrophy and a loss of white matter volume.^[5]

Through Lifespan

Facial dysmorphism and subtle skeletal features are common in younger children.^[5] The condition progressively worsens, as spasticity and distal amyotrophy symptoms are revealed more in teenage years.^[5] SPG20 expression in the adult is relatively modest, however it is widespread in the nervous system.^[5] Longitudinal comparison of magnetic resonance imaging concluded that there was a progression of the syndrome; thus, the condition appears to worsen over time.^[5]

References

1. Cross HE, McKusick VA (Jun 1967). "The Troyer syndrome. A recessive form of spastic paraplegia with distal muscle wasting". Arch Neurol 16 (5): 473–85. doi:10.1001/archneur.1967.00470230025003. PMID 6022528.
2. Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH (Jul 2002). "SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia". Nat Genet 31 (4): 347–8. doi:10.1038/ng937. PMID 12134148.
3. "Entrez Gene: SPG20 spastic paraplegia 20, spartin (Troyer syndrome)".
4. Bakowska, J.C., Jenkins, R., Pendleton, J., Blackstone, C. (2005). "The Troyer syndrome (SPG20) protein interacts with Eps15". Biochemical and Biophysical Research Communications 334 (4): 1042–1048. doi:10.1016/j.bbrc.2005.06.201. PMID 16036216.
5. Manzini, M. C., Rajab, A., Maynard, T. M., Mochida, G. H., Tan, W., Nasir, R., . . . Walsh, C.A. (2010). "Developmental and degenerative features in a complicated spastic paraplegic.". Annals of Neurology 67: 516–525. doi:10.1002/ana.21923.

External links

• GeneReviews/NCBI/NIH/UW entry on Troyer Syndrome **

Further reading

• Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags.". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
• Nagase T, Ishikawa K, Miyajima N, et al. (1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.". DNA Res. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581.
• Auer-Grumbach M, Fazekas F, Radner H, et al. (1999). "Troyer syndrome: a combination of central brain abnormality and motor neuron disease?". J. Neurol. 246 (7): 556–61. doi:10.1007/s004150050403. PMID 10463356.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ciccarelli FD, Proukakis C, Patel H, et al. (2003). "The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia.". Genomics 81 (4): 437–41. doi:10.1016/S0888-7543(03)00011-9. PMID 12676568.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13.". Nature 428 (6982): 522–8. doi:10.1038/nature02379. PMC 2665288. PMID 15057823.
• Liu M, Liu Y, Cheng J, et al. (2004). "Transactivating effect of hepatitis C virus core protein: a suppression subtractive hybridization study.". World J. Gastroenterol. 10 (12): 1746–9. PMID 15188498.
• Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Bakowska JC, Jenkins R, Pendleton J, Blackstone C (2005). "The Troyer syndrome (SPG20) protein spartin interacts with Eps15.". Biochem. Biophys. Res. Commun. 334 (4): 1042–8. doi:10.1016/j.bbrc.2005.06.201. PMID 16036216.
• Lu J, Rashid F, Byrne PC (2006). "The hereditary spastic paraplegia protein spartin localises to mitochondria.". J. Neurochem. 98 (6): 1908–19. doi:10.1111/j.1471-4159.2006.04008.x. PMID 16945107.
• Bakowska JC, Jupille H, Fatheddin P, et al. (2007). "Troyer syndrome protein spartin is mono-ubiquitinated and functions in EGF receptor trafficking.". Mol. Biol. Cell 18 (5): 1683–92. doi:10.1091/mbc.E06-09-0833. PMC 1855030. PMID 17332501.
• Bakowska, J.C., Jenkins, R., Pendleton, J., Blackstone, C. (2005). "The Troyer syndrome (SPG20) protein interacts with Eps15". Biochemical and Biophysical Research Communications 334 (4): 1042–1048. doi:10.1016/j.bbrc.2005.06.201. PMID 16036216.
• Manzini, M. C., Rajab, A., Maynard, T. M., Mochida, G. H., Tan, W., Nasir, R., . . . Walsh, C.A. (2010). "Developmental and degenerative features in a complicated spastic paraplegic.". Annals of Neurology 67: 516–525. doi:10.1002/ana.21923.
• Ciccarelli, F. D., Patton, M. A., McKusick, V. A., Crosby, A. H. (2002). "SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia.". Nature Genetics 31 (4): 347–348. doi:10.1038/ng937. PMID 12134148.