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

Обзор

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.

Вмешательства

• Генная терапия RNA and/or DNA methylation and/or protein analysis
  RNA and/or DNA methylation and/or protein analysis from a blood sample or another tissue including dedifferenciation into induced pluripotent stem cells

Первичные конечные точки

• number and proportion of patients [Срок оценки: through study completion, an average of 5 years]

Вторичные конечные точки (2)

• Inclusion [Срок оценки: through study completion, an average of 5 years]
• Identification of at least one candidate biomarker linked to one or more abnormalities of a gene or group of genes. [Срок оценки: through study completion, an average of 5 years]

Критерии участия

Критерии включения

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.

Критерии исключения

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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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Франция · 1 центр

• Rouen University Hospital — Rouen

Идентификаторы

NCT: NCT06955624 · 2024/0190/HP · 2024-A01559-38

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗