Spastic Paraplegia 7 Proteins (SPG7)

Human Spastic Paraplegia 7 (SPG7) interaction partners

1. SPG7 mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late-onset pure ataxia

2. Compound heterozygous variants in SPG7 identified in 22 French Canadian patients with spastic ataxia.

3. CACNA1A and SPG7 are major ataxia genes.

4. The results of this study showed that the most frequently detected variant in this cohort was the SPG7 p.Leu78.

5. A Norwegian founder mutation p.H701P is a major cause of SPG7 in Norway.

6. a novel homozygous frameshift deletion in the SPG7 gene was identifies as the genetic cause of hereditary spastic paraplegia in a Greek family.

7. this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology.

8. Data indicates that SPG7 is essential for the mitochondrial permeability transition pore (PTP) complex formation, interacts with CypD and VDAC and determines C terminus of SPG7 and CsA-binding region of CypD as necessary for PTP formation.

9. In unexplained ataxia, there was a significant number of patients with SPG7 mutations.

10. The SPG7 Q866 variant is efficiently processed independent of phosphorylation of AFG3L2 at Y179, which inhibits processing of SPG7.

11. Using an unbiased exome sequencing approach we identified pathogenic compound heterozygous SPG7 mutations in patients with PEO and multiple mitochondrial DNA deletions in skeletal muscle

12. A Japanese patient is reported with an SPG7 mutation for a slowly progressive form of autosomal recessive cerebellar ataxia and spastic paraplegia.

13. This study showed that the p.Ala510Val mutation is prevalent amongst severe hereditary spastic paraparesis patients of UK.

14. Data suggest a pathogenic role for this SPG7 p.A510V variant.

15. SPG7 mutations correlate with spastic paraplegia phenotypes.

16. SPG7 mutations are a frequent cause of middle-aged onset of spastic gait when strict inclusion criteria are applied and should, therefore, be tested in autosomal recessive or sporadic hereditary spastic paraplegia.

17. Studies indicate that both mouse and human SPG7 ESTs containing alternative first exons.

18. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss-of-function of the paraplegin-AFG3L2 complex in the mitochondrial inner membrane.

19. structural analysis of the ATPase domain of the human AAA+ protein paraplegin/SPG7

20. mutation in spastin and paraplegin genes does not appear to cause motor neuron disease

Mouse (Murine) Spastic Paraplegia 7 (SPG7) interaction partners

1. Studies indicate that both mouse and human SPG7 ESTs containing alternative first exons.

2. These results provide evidence for different substrate specificities of m-AAA proteases and reveal a striking evolutionary switch of proteases involved in the proteolytic processing of dynamin-like GTPases in mitochondria.

3. Data show that Afg3l1 or Afg3l2 are required for maturation of newly imported paraplegin subunits after their cleavage by MPP.

4. Spg7 and Afg3l2 double mutants show an early-onset ataxic phenotype, indicating a role of the m-AAA proteases in cerebellar degeneration.