The SPG20 gene encodes a protein of 666 amino acids with molecular weight of about 73 kDa. The Spartin protein contains a Microtubule-Interacting and Trafficking molecule (MIT) domain in the N-terminus. It localizes to mitochondria and partially co-localizes with microtubules. Spartin is a multifunctional protein, implicated in regulating endosomal trafficking and mitochondria function. It has multiple alternative splice variants, encoding the same protein. Defects in this protein are the cause of autosomal recessive spastic paraplegia 20 (Troyer syndrome), characterized by dysarthria, distal amyotrophy, mild developmental delay and short stature.
The SPG20 gene is located on chromosome 13q13.3, consists of eight coding exons, and spans approximately 69 kb. The mutated SPG20 gene has been shown to cause the autosomal recessive spastic paraplegia-20 (Troyer syndrome). One mutation has been identified in people with Troyer syndrome. This is a 1-bp deletion (1110delA) that results in an abnormally shortened, nonfunctioning Spartin protein.
Manzini et al. (2010) screened the SPG20 gene in two affected Omani families with Troyer syndrome. A novel homozygous two base pair deletion (c.364-365delAT) was identified in the coding region of the SPG20 gene in all affected individuals, resulting in an amino acid substitution followed by a stop codon in the first coding exon. Lymphoblastoid cell lines showed that full-length Spartin protein was not found in the affected individuals. In addition, qPCR revealed that there was no mRNA, suggesting that this mutation is a null allele. This mutation is different from the one that was found among Amish patients; nevertheless, both mutations resulted in the phenotypic spectrum associated with Troyer syndrome. These finding indicates that Troyer syndrome is not restricted to the Amish population as it was reported.