Clinical trial NCT06955624: Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases
Official title: Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neurogenetic Diseases
Keywords: Neurogenetic diseases
Central nervous system disease
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
Collaborators: name: University Hospital, Lille
name: Groupe Hospitalier Pitie-Salpetriere
First posted: 2025-05-02
Enrollment: 95
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Qualification: Category 2 Product or procedure: excluding health products (products not mentioned in Article L.5311-11 of the Public Health Code)
Primary purpose: DIAGNOSTIC

Brief summary: Many neurological disorders show a strong genetic basis, from hereditary diseases caused by a single mutation in a given gene, to diseases caused by combinations of strong genetic risk factors. However, even after the sequencing of the appropriate genes, a large proportion of patients remains undiagnosed, either because there is no candidate mutation observed, or in case of identification of a candidate mutation with insufficient knowledge to consider it as pathogenic or not.

The aim of this project is to identify the cause of neurogenetic diseases in patients in situations of diagnostic wandering or dead ends by proposing the analysis of RNA and/or proteins from different tissues.


Eligibility criteria: Inclusion Criteria:

For this project, the inclusion of 3 participant profiles is required:

* 1a. Patient, major or minor, with a neurological disease affecting the central nervous system, who has already benefited from a genomic analysis (panel, exome or genome sequencing) as part of routine care, with inconclusive analysis because the result was either a variation of uncertain significance or the absence of a variant of interest (patients with inconclusive genomic results).
* 1b. Patient with neurological disease affecting the central nervous system, of confirmed monogenic or probable oligogenic cause (positive controls).
* A relative of a type 1a. or 1b. patient with no symptoms of the disease, after the expected age of onset of symptoms in the patient's own family (healthy relatives).

For all 3 groups:

* Affiliation with a social security scheme
* Agreement to take part in the study with signature of a specific informed consent form for the study.

Exclusion Criteria:

For patients with inconclusive results: Patient with a neurological disease not suspected of a monogenic or oligogenic cause

For healthy relatives: existence of a neurological disease (other than uncomplicated migraine) or psychiatric disease (other than simple anxiety stable under treatment).

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Primary outcomes:
measure: number and proportion of patients
timeFrame: through study completion, an average of 5 years
Secondary outcomes:
measure: Inclusion
timeFrame: through study completion, an average of 5 years
measure: Identification of at least one candidate biomarker linked to one or more abnormalities of a gene or group of genes.
timeFrame: through study completion, an average of 5 years
Other outcomes:
Locations:
city: Rouen
country: France
facility: Rouen University Hospital
Study officials:
References: