Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases

Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases

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.

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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