- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05127967
Consequences of Mutations in the SPG7 Gene at the Heterozygous State (CONSP-HET7)
Phenotypic, Biological and Functional Consequences of Mutations in the SPG7 Gene at the Heterozygous State
Study Overview
Detailed Description
Although spastic paraplegia type 7 is considered to be a recessive disease, some clinical observations also argue for 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. To date there have been no studies to specifically explore the pathogenic role of single heterozygous variants in the SPG7 gene.
The aim of this project is to fully characterize different models expressing single heterozygous SPG7 mutations in order to detect phenotypical, biological or functional alterations. In particular, the investigators will conduct analysis on fibroblasts from symptomatic patients with mutations in the SPG7 gene (homozygous, compound heterozygous or single heterozygous), and controls. Cellular models will be particularly useful in order to study an alteration in calcium homeostasis and in the response to ER stressors. In parallel, studies will be performed using the genetic animal model of Drosophila melanogaster.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Herault
-
Montpellier, Herault, France, 34000
- Montpellier University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Case inclusion criteria
- 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
Inclusion criteria for controls
- 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)
Non-inclusion Criteria of cases
- 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
Non-inclusion Criteria of controls
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Patients with neurological symptoms and two mutations in the SPG7 gene
Symptomatic patients with SPG7 mutations (homozygous or compound heterozygous)
|
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.
|
Other: Patients with neurological symptoms and one mutation in the SPG7 gene
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
|
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.
|
Other: Controls
Patients without mutations in the SPG7 gene requiring spinal surgery because of a non-genetic neurologic disorders
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: Inclusion
|
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
Time Frame: Inclusion
|
Inclusion
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: Inclusion
|
Inclusion
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- RECHMPL20_0615
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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