Consequences of Mutations in the SPG7 Gene at the Heterozygous State

  • STATUS
    Recruiting
  • End date
    Oct 7, 2024
  • participants needed
    18
  • sponsor
    University Hospital, Montpellier
Updated on 7 January 2022

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.

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.

Details
Condition SPG7
Treatment Skin Biopsy
Clinical Study IdentifierNCT05127967
SponsorUniversity Hospital, Montpellier
Last Modified on7 January 2022

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note