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). Troyer syndrome (SPG20) is a complicated type of hereditary spastic paraplegias (HSPs). HSP is a category of neurological disorder characterized by spasticity and muscle weakness in the lower limbs.
The original description of this gene mutation and associated symptoms were described in 1967. 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.
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.
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.
^ abcBakowska, 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. PMID16036216. doi:10.1016/j.bbrc.2005.06.201.
^ abcdefghijkManzini, 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: 516–525. doi:10.1002/ana.21923.
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. PMID8889549. doi:10.1101/gr.6.9.807.
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. PMID9628581. doi:10.1093/dnares/5.1.31.
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. PMID10463356. doi:10.1007/s004150050403.
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. PMID12676568. doi:10.1016/S0888-7543(03)00011-9.
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. PMID14702039. doi:10.1038/ng1285.
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. PMID16036216. doi:10.1016/j.bbrc.2005.06.201.
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: 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. PMID12134148. doi:10.1038/ng937.