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]
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]
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
↑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. PMID6022528.
↑ 2.02.1Patel 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. PMID12134148.
↑ 4.04.14.2Bakowska, 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. PMID16036216.
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. PMID8889549.
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. PMID9628581.
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. PMID10463356.
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. PMID12676568.
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. PMID14702039.
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. PMID16036216.
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. PMID16945107.
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. PMID16036216.
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. PMID12134148.
