Consequences of Mutations in the SPG7 Gene at the Heterozygous State

NCT05127967 | Completed

• 1 other identifier: RECHMPL20_0615
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Paraplegin, encoded by the SPG7 gene, is an ATP-dependent mAAA protease located in the inner mitochondrial membrane. Its function is not fully understood. Mutations in the SPG7 gene are responsible for spastic paraplegia type 7. Although spastic paraplegia type 7 is considered to be a recessive disease, some clinical observations also point to a detrimental effect of a variant in SPG7 in the heterozygous state. Thus, the presence of a single mutated variant of the SPG7 gene could be a risk factor for the development of neurological diseases. This has important implications for genetic counseling of patients and for the understanding of the function of the SPG7 protein and the mechanisms of disease development.

Conditions

SPG7

Keywords

SPG7; Dominant; human; Drosophila; mitochondria

Outcome Measures

Primary Outcomes (2)

• Mitochondrial respiratory activity measured by Seahorse analyser and quantification of mADN vs nuclear AND in activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls

  Inclusion

• Mitochondrial dimension and morphology by electronic microscopy and quantification of mitochondrial motility by direct imaging activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls

  Inclusion

Secondary Outcomes (1)

• Mitochondrial calcium quantification after expression of a probe for calcium detection in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls

  Inclusion

Study Arms (3)

Patients with neurological symptoms and two mutations in the SPG7 gene

OTHER

Symptomatic patients with SPG7 mutations (homozygous or compound heterozygous)

Other: Skin biopsy

Patients with neurological symptoms and one mutation in the SPG7 gene

OTHER

Patients presenting neurological symptoms corresponding to SPG7 disease (adult onset spastic ataxia with CPEO and/or optic atrophy) with only one mutation found in the SPG7 gene

Other: Skin biopsy

Controls

OTHER

Patients without mutations in the SPG7 gene requiring spinal surgery because of a non-genetic neurologic disorders

Other: Skin biopsy

Interventions

Skin biopsy OTHER

A skin biopsy involves taking a piece of skin to obtain cells (fibroblasts). Skin biopsy is a minimally invasive examination and a technically simple procedure performed with a 3mm diameter punch, or with a scalpel under local anesthesia (Lidocaine patch). The procedure can be done in a consultation office with strict asepsis. It lasts 15 minutes in total + the time to reach between putting on the lidocaine patch and performing the procedure. This biopsy will usually be done on the inside of the arm. In the majority of cases, it is not helpful to close the scar with stitches.

Controls; Patients with neurological symptoms and one mutation in the SPG7 gene; Patients with neurological symptoms and two mutations in the SPG7 gene

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \> or equal to 18 years
• presence of neurological symptoms compatible with GSP7 (ataxia, spasticity progressive external ophthalmoplegia, and/or optic atrophy)
• presence of two mutations in the SPG7 gene (= recessive forms of SPG7) or of a single mutation in the simple heterozygous state in the absence of other genetic factors explaining the symptoms
• Age \> or equal to 18 years
• Subject who is already undergoing neurosurgical intervention as part of the care pathway for an for an acquired, non-genetic neurological problem (e.g. herniated disc, narrow lumbar canal)
• Refusal to sign the written informed consent signed by the patient (or by his representative in case of a patient under guardianship.
• Patients with specific contraindications for skin biopsy current anticoagulant treatment; any pathologies that may cause a risk of bleeding (e.g. hemophiliacs)
• Refusal of the patient, of the guardian if necessary, to sign the informed consent to participate in the in the research
• Not being a beneficiary of a social protection plan Patient deprived of liberty
• Patients with a genetic neurological disease or mitochondrial disease
• Patients with specific contraindications for skin biopsy: current anticoagulant treatment; all pathologies that may cause a risk of bleeding (e.g. hemophilia)
• Refusal to sign the informed consent to participate in the research
• Not benefiting from a social protection plan
• Patient deprived of liberty
• Patient under guardianship or curatorship

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Montpellier University Hospital

Montpellier, Herault, 34000, France

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 19, 2021
• Study Start: November 16, 2021
• Primary Completion: January 26, 2022
• Study Completion: January 26, 2022
• Last Updated: February 17, 2023

Record last verified: 2023-02

Locations

FR (1)