Spastic Paraplegia 4, Autosomal Dominant (SPAST)
| Dred_ID | RD00011 |
| OMIM ID | 182601 |
| Disease name | Spastic Paraplegia 4, Autosomal Dominant |
| Alternative names | Hereditary Spastic Paraplegia, Spastin Type SPAST-Associated HSP SPG4 |
| Category | Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Gastrointestinal diseases, Bone diseases, Mental diseases, Metabolic disease |
| Phenotype | OMIM: The hereditary spastic paraplegias (SPG, HSP) are a group of clinically and genetically diverse inherited disorders characterized predominantly by progressive lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated') or with other neurologic abnormalities ('complicated'). Pure SPG4 is the most common form of autosomal dominant hereditary SPG, comprising up to 45% of cases (Svenson et al., 2001; Crippa et al., 2006). |
| Miscellaneouse | OMIM: progressive disorder genetic anticipation insidious onset highly variable severity variable age of onset (infancy to 63 years) most common form of autosomal dominant hereditary spastic paraplegia (accounts for 40% of spg cases) genetic heterogeneity, see spg3a |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | SPAST |
| Alias symbols | FSP2; SPG4; ADPSP |
| Gene name | spastin |
| Gene map locus | 2p22.3; chr2:32,063,551-32,157,637(+) |
| Ensembl Gene ID | ENSG00000021574 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP |
| Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The encoded ATPase may be involved in the assembly or function of nuclear protein complexes. Two transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their full length sequences have not been determined. Mutations associated with this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. [provided by RefSeq, May 2018] |
| Repeat unit | CAG |
| Normal repeat copies | <16 |
| Pathogenic repeat copies | ≥61 |
| Gene | SPAST |
| Repeat location | CDS |
| Chromosome locus | chr2:32073783-32073791 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | Mitne-Neto et al. (2007) identified a heterozygous tandem duplication of exons 10 through 12 of the SPG4 gene (604277.0022) in affected individuals of a large Brazilian kindred with spastic paraplegia, originally reported by Starling et al. (2002). In this family, Starling et al. (2002) noted that there were 24 affected men and only 1 affected woman, but X-linked inheritance was ruled out. The authors found strong linkage to the SPG4 locus, but no mutations were identified in the coding region of the SPG4 gene. The results of Mitne-Neto et al. (2007) thus confirmed the diagnosis of SPG4. At the time of the latter report, 12 of 30 mutation carriers had no clinical complaints. Among these patients, 9 of 14 female carriers had no complaints, indicating sex-dependent penetrance in this family, with women being partially protected. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 9736780 |
| Authors | Benson KF, Horwitz M, Wolff J, Friend K, Thompson E, White S, Richards RI, Raskind WH, Bird TD |
| Title | CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients |
| Journal | Hum Mol Genet. 7(11):1779-86 |
| Year | 1998 |