SPG20

{{Short description|Protein-coding gene in the species Homo sapiens}}

Spartin is a protein that in humans is encoded by the SPG20 gene.{{cite journal | vauthors = Cross HE, McKusick VA | title = The Troyer syndrome. A recessive form of spastic paraplegia with distal muscle wasting | journal = Arch Neurol | volume = 16 | issue = 5 | pages = 473–85 |date=Jun 1967 | pmid = 6022528 | doi = 10.1001/archneur.1967.00470230025003}}{{cite journal | vauthors = Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH | title = SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia | journal = Nat Genet | volume = 31 | issue = 4 | pages = 347–8 |date=Jul 2002 | pmid = 12134148 | doi = 10.1038/ng937 | s2cid = 23051225 }}{{cite web | title = Entrez Gene: SPG20 spastic paraplegia 20, spartin (Troyer syndrome)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23111}}

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.{{cite journal|author=Chiara Diquigiovanni |author2=Christian Bergamini |author3=Rebeca Diaz |author4=Irene Liparulo |author5=Francesca Bianco |author6=Luca Masin |author7=Vito Antonio Baldassarro |author8=Nicola Rizzardi |author9=Antonia Tranchina |author10=Francesco Buscherini |author11=Anita Wischmeijer |author12=Tommaso Pippucci |author13=Emanuela Scarano |author14=Duccio Maria Cordelli |author15=Romana Fato |author16=Marco Seri |author17=Silvia Paracchini |author18=Elena Bonora |title=A novel mutation in SPART gene causes a severe neurodevelopmental delay due to mitochondrial dysfunction with complex I impairments and altered pyruvate metabolism|journal=FASEB Journal|date=7 August 2019|volume=33|issue=10|pages=11284–11302|doi=10.1096/fj.201802722R|pmid=31314595|doi-access=free|hdl=10023/18172 |hdl-access=free }} Frameshift mutations associated with this gene cause autosomal recessive spastic paraplegia 20 (Troyer syndrome).

Troyer syndrome (SPG20) is a complicated type of hereditary spastic paraplegias (HSPs).{{cite journal | author = Bakowska, J.C. | author2 = Jenkins, R. | author3 = Pendleton, J. | author4 = Blackstone, C. |title = The Troyer syndrome (SPG20) protein interacts with Eps15 |journal = Biochemical and Biophysical Research Communications |volume = 334 |pages = 1042–1048 |year = 2005 |pmid = 16036216|doi = 10.1016/j.bbrc.2005.06.201|issue=4|url = https://zenodo.org/record/1258788 }} HSP is a category of neurological disorder characterized by spasticity and muscle weakness in the lower limbs.

Background

The original description of this gene mutation and associated symptoms were described in 1967.{{cite journal |author = Manzini, M. C. |author2 = Rajab, A. |author3 = Maynard, T. M. |author4 = Mochida, G. H. |author5 = Tan, W. |author6 = Nasir, R. |display-authors = etal |title = Developmental and degenerative features in a complicated spastic paraplegic. |journal = Annals of Neurology |volume = 67 |issue = 4 |pages = 516–525 |year = 2010 |pmid = 20437587|doi = 10.1002/ana.21923|pmc = 3027847}} This mutation is commonly found in high frequency with the Amish population. Newer studies have found that the mutation is not isolated to the Amish population, but also resides in the Omani population.

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.

=Physical=

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

=Cognitive=

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

=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.

=Diagnostic Imaging=

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

=Through Lifespan=

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

References

External links

[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=spg20 GeneReviews/NCBI/NIH/UW entry on Troyer Syndrome] **

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{{cite journal | vauthors=Bakowska JC, Jenkins R, Pendleton J, Blackstone C |title=The Troyer syndrome (SPG20) protein spartin interacts with Eps15. |journal=Biochem. Biophys. Res. Commun. |volume=334 |issue= 4 |pages= 1042–8 |year= 2005 |pmid= 16036216 |doi= 10.1016/j.bbrc.2005.06.201 |url=https://zenodo.org/record/1258788 }}
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{{cite journal | author = Bakowska, J.C. | author2 = Jenkins, R. | author3 = Pendleton, J. | author4 = Blackstone, C. |title = The Troyer syndrome (SPG20) protein interacts with Eps15 |journal = Biochemical and Biophysical Research Communications |volume = 334 |pages = 1042–1048 |year = 2005 |pmid = 16036216|doi = 10.1016/j.bbrc.2005.06.201|issue=4|url = https://zenodo.org/record/1258788 }}
{{cite journal |author = Manzini, M. C. |author2 = Rajab, A. |author3 = Maynard, T. M. |author4 = Mochida, G. H. |author5 = Tan, W. |author6 = Nasir, R. |display-authors = etal |title = Developmental and degenerative features in a complicated spastic paraplegic. |journal = Annals of Neurology |volume = 67 |issue = 4 |pages = 516–525 |year = 2010 |pmid = 20437587|doi = 10.1002/ana.21923|pmc = 3027847}}
{{cite journal |author = Ciccarelli, F. D. |author2 = Patton, M. A. |author3 = McKusick, V. A. |author4 = Crosby, A. H. |title = SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. |journal = Nature Genetics |volume = 31 |pages = 347–348|year = 2002 |pmid = 12134148|doi = 10.1038/ng937|issue=4|s2cid = 23051225 }}