Targeted Next Generation Sequencing and Intellectual Disability

Study Overview
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Brief Summary
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The purpose is to determine the benefit of next generation sequencing (NGS) targeted on genes involved in intellectual disability for etiologic diagnosis of intellectual disabilities. In other words, it concerns the number of patients whose etiologic diagnosis will be established with NGS and could not with common techniques. Actually, the molecular etiology of intellectual disability is crucial to calculate the risk of recurrence and allows the perinatal diagnosis to these families. Secondary purposes are: To determine the place of NGS in the strategy of etiologic diagnosis of intellectual disability, to determine the order of analyses performed for a patient with intellectual disability without clinical signs. To evaluate the number of variants with unknown significance and thus non-usable for genetic counselling without supplementary analysis. To determine the number of samples that can be at most pooled keeping a good efficacy of capture and results with suitable read depth To determine the possibility of detecting copy number variations (CNVs) in genes of interest with NGS To establish genotype/phenotype correlations for each gene for which a mutation has been identified To optimize the software pipelining for a rapid analysis for diagnosis.

Official Title
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Targeted Next Generation Sequencing and Intellectual Disability

Conditions
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Intellectual Disability

Intervention / Treatment
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* Other: Blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate or severe intellectual disability Availability of patient and parent DNA No etiologic diagnosis with standard approaches: negative fragile X, normal pangenomic 180K and 1M array-CGH Informed consent of person having parental authority Exclusion Criteria: Non availability of parent DNA Patient lost to follow-up
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intellectual disability<br> | Other: Blood sample<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with certain etiologic diagnosis established with NGS |  | day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with etiologic diagnosis established with NGS or with other techniques (array-CGH) |  | day 0 | 
| Obtained read depth according to number of pooled samples |  | day 0 | 
| Percentage of patients with variant with unknown significance, needing supplementary analyses to prove its involvement in intellectual disability |  | day 0 | 
| CNVs detected with NGS or array-CGH (reference technique for CNV detection). |  | day 0 | 
| Clinical phenotype for each gene for which a causal mutation is identified by NGS |  | day 0 | 
| Time of analysis of NGS raw data |  | day 0 |