Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic

Study Overview
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Brief Summary
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Intellectual disability (ID) moderate or severe affects about one child in 250, with 3000 to 4000 new cases each year. Chromosomal or molecular pathology causes are not identified in half of the cases by current techniques. Studies show that de novo mutations are common in many different genes. The exome approach by high-throughput sequencing (NGS) has emerged as the technique of choice for identifying and comparing the exome of the child to the parent. We wish to evaluate this approach and its contribution in the diagnostic management of 50 patients with DI seen in genetics in 6 CHU Great West. Genomics platform IBISA / Biogenouest will provide technological and bioinformatics support this project.

Official Title
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Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic

Conditions
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Severe Intellectual Disability

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe intellectual disability (IQ <35 ) or moderate (IQ <50) isolated or syndromic presentation but undiagnosed . The diagnosis is established during genetic counseling of a 6 CHU interregion Lack of family history ( parents). We are interested in this project to patients who do not have family history in order to increase the probability of identifying a de novo mutation . We do not however exclude the hypothesis for some patients a mechanism recessive autosomal or X-linked . Recruitment in 6 CHU HUGO . Patients are required to have been seen in genetics in a 6 CHU interregion . Molecular analyzes of the Fragile X syndrome and the CGH technique must be negative. Indication sequencing exomique adopted by the Scientific Committee. The Scientific Committee HUGODIMS project role to select patients whose DNA will be studied in order to optimize the chances of success for sequencing . This selection must take into account clinical parameters , but also genetic parameters ( potential inbreeding ) . The files will be selected by videoconferencing at the end of the monthly meeting of CLAD . The methodologist of the study will be invited to videoconferencing. specific consent obtained for the study. Exclusion Criteria: Parents patient with moderate or severe intellectual disability disagree with the preferred hypothesis of de novo mutation or recessive transmission mechanism. Form with known syndromic diagnosis can be targeted molecular studies (clinical signs). Cause molecular DI identified by targeted molecular analysis or CGH. Explicit refusal to participate in the study of the patient, parents, or one of the two parents. Any other indication that intellectual disability. The parents of the patient or the patient may be removed.
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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients for which a mutation responsible for the de novo patients DI has been identified |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients for whom the study of exomes revealed mutations in genes compatible with the mode of recessive autosomal recessive or X-linked chromosome |  | 18 months | 
| Number of de novo mutations (loss of function, missense or indels) probably pathogens identified are not known to be involved in the DI genes. |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe intellectual disability, genetic, de novo exome