SPG7 encodes a nuclear-encoded mitochondrial metalloprotease protein termed paraplegin.

Pathology

 germline SPG7 mutations in SPG7-associated hereditary spastic paraplegia

• autosomal recessive hereditary pure spastic paraplegia
• linkage and subsequent mutation analysis revealed large deletions in SPG7

 Muscle biopsies from the autosomal recessive form of patients with hereditary spastic paraplegia revealed histochemical signs of a mitochondrial disorder, namely RRFs, COX-negative fibres and succinate dehydrogenase-positive hyperintense fibres.

 Owing to the homology with a yeast mitochondrial ATPase with both proteolytic and chaperone-like activities, it has been suggested that this form of hereditary spastic paraplegia could be a neurodegenerative disorder due to OXPHOS deficiency, attributing a putative function in the assembly or import of respiratory chain subunits or cofactors to paraplegin.

See also

 hereditary spastic paraplegias

• SPG7-associated hereditary spastic paraplegia

References

 Shoubridge EA. Nuclear genetic defects of oxidative phosphorylation. Hum Mol Genet. 2001 Oct 1;10(20):2277-84. PMID: #11673411#

 Smeitink J, van den Heuvel L, DiMauro S. The genetics and pathology of oxidative phosphorylation. Nat Rev Genet. 2001 May;2(5):342-52. PMID: #11331900#