Functional Study of Rare Disease Related Candidate Genes - ORIGIN

Study Overview
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Brief Summary
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Next generation sequencing (NGS) allows some better diagnostic results, particularly, in the rare diseases field. At a twenty five percent rate, those exams highlight some variants which are not yet described in human pathology. The relationship between a variant found inside a candidate gene and a pathology, is able to be confirmed by functional studies at a protein level. This study aims to build a biological collection to feed further functional studies to confirm the relationship between NGS identified variants, and the clinical signs and symptoms.

Official Title
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Functional Study of Rare Disease Related Candidate Genes - ORIGIN

Conditions
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Rare Diseases, Genetic Disease

Intervention / Treatment
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* Procedure: Skin biopsy, blood sample, urine sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient : Child or adult affected by a rare disease and with an identified variant in a candidate gene whose molecular functions are not known, or whose pathophysiologic mechanism are not fully understood. Patient included inside the BaMaRa (French rare disease national data bank) database dedicated to the rare diseases. Patient Affiliated to the French social security system. Patient consent form or legal representative consent form obtained. Patient's parent : Parent of a patient affected by a rare disease and with identified variant in a candidate gene whose molecular functions are not known, or whose pathophysiologic mechanism are not fully understood. Parent included in the BaMaRa database. Parent affiliated to the French social security system. Parent consent form obtained for himself/herself. Patient's brother or sister : Brother or sister of a patient (underage or adult) affected by a rare disease and with identified variant in a candidate gene whose molecular functions are not known, or whose pathophysiologic mechanism are not fully understood. Brother or sister included in the BaMaRa database. Brother or sister affiliated to the French social security system. Brother or sister consent form obtained for themselves or from their legal representative. Exclusion Criteria: Poor understanding of the French language Legal of administrative liberty deprivation Psychiatric force care
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: In addition to the standard clinical care, blood samples and/or urine samples and/or skin biopsy will be proposed to the included patient to carry out further genetic analysis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>Specific interventions: Blood samples, skin biopsy, urine collection or operational waste qualified as research sample. | Procedure: Skin biopsy, blood sample, urine sample<br>* blood samples, urine samples, skin samples.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of at least 80 new genes implicated in rare diseases via high-throughput sequencing technics and through functional studies. | Candidate genes, suspected to be responsible for rare diseases will be identified before the inclusion, during standard medical care, by exome or genome sequencing. | 23 years | 
| Collecting biological samples to build up a biobank | After a candidat gene identification, patient will be proposed sampling (blood or urine) or if a skin biopsy, an amniotic fluid puncture or any surgery are done during standard care, the remaing tissue or fluid, or operative wastes will be eligible too, to be stored in the biobank. | 23 years | 
| Candidat gene validation through functional studies. | Biological samples from the biobank will be made available after the study, to some specialized research teams, in order to validate or overturn those previously gene candidates by the way of some biological technics. | 23 years |