SPG20

Spartin is a protein that in humans is encoded by the SPG20 gene.[3][4][5]

SPART
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesSPART, SPARTIN, TAHCCP1, SPG20, spastic paraplegia 20 (Troyer syndrome)
External IDsOMIM: 607111 HomoloGene: 32243 GeneCards: SPART
Orthologs
SpeciesHumanMouse
Entrez

23111

n/a

Ensembl

ENSG00000133104

n/a

UniProt

Q8N0X7

n/a

RefSeq (mRNA)

NM_001142294
NM_001142295
NM_001142296
NM_015087

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 13: 36.3 – 36.37 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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. Spartin loss has been associated to mitochondrial dysfunction, impaired complex I activity and altered pyruvate metabolism.[6] Frameshift mutations associated with this gene cause autosomal recessive spastic paraplegia 20 (Troyer syndrome).[5] Troyer syndrome (SPG20) is a complicated type of hereditary spastic paraplegias (HSPs).[7] HSP is a category of neurological disorder characterized by spasticity and muscle weakness in the lower limbs.[7]

Background

The original description of this gene mutation and associated symptoms were described in 1967.[8] This mutation is commonly found in high frequency with the Amish population.[4] Newer studies have found that the mutation is not isolated to the Amish population, but also resides in the Omani population.[8]

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.[7]

Physical

Individuals appear to have difficulty walking, and report a clumsy, spastic gait which worsens over time.[8] Some additional common physical features include overgrowth of the jaw bone, hammer toes, hand and feet abnormalities, and pes cavus.[8]

Cognitive

Cognitive challenges, including developmental delay and difficulty with performance in school, may affect individuals with this syndrome.[8]

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.[8]

Diagnostic Imaging

The cerebellar vermis may present with mild atrophy and a loss of white matter volume.[8]

Through Lifespan

Facial dysmorphism and subtle skeletal features are common in younger children.[8] The condition progressively worsens, as spasticity and distal amyotrophy symptoms are revealed more in teenage years.[8] SPG20 expression in the adult is relatively modest, however it is widespread in the nervous system.[8] Longitudinal comparison of magnetic resonance imaging concluded that there was a progression of the syndrome; thus, the condition appears to worsen over time.[8]

References
  1. GRCh38: Ensembl release 89: ENSG00000133104 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 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.
  4. 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. S2CID 23051225.
  5. "Entrez Gene: SPG20 spastic paraplegia 20, spartin (Troyer syndrome)".
  6. Chiara Diquigiovanni; Christian Bergamini; Rebeca Diaz; Irene Liparulo; Francesca Bianco; Luca Masin; Vito Antonio Baldassarro; Nicola Rizzardi; Antonia Tranchina; Francesco Buscherini; Anita Wischmeijer; Tommaso Pippucci; Emanuela Scarano; Duccio Maria Cordelli; Romana Fato; Marco Seri; Silvia Paracchini; Elena Bonora (7 August 2019). "A novel mutation in SPART gene causes a severe neurodevelopmental delay due to mitochondrial dysfunction with complex I impairments and altered pyruvate metabolism". FASEB Journal. 33 (10): 11284–11302. doi:10.1096/fj.201802722R. PMID 31314595.
  7. 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.
  8. Manzini, M. C.; Rajab, A.; Maynard, T. M.; Mochida, G. H.; Tan, W.; Nasir, R.; et al. (2010). "Developmental and degenerative features in a complicated spastic paraplegic". Annals of Neurology. 67 (4): 516–525. doi:10.1002/ana.21923. PMC 3027847. PMID 20437587.

Further reading


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