Intellectual Disability
Conditions
Brief summary
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: 1. 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. 2. To evaluate the number of variants with unknown significance and thus non-usable for genetic counselling without supplementary analysis. 3. To determine the number of samples that can be at most pooled keeping a good efficacy of capture and results with suitable read depth 4. To determine the possibility of detecting copy number variations (CNVs) in genes of interest with NGS 5. To establish genotype/phenotype correlations for each gene for which a mutation has been identified 6. To optimize the software pipelining for a rapid analysis for diagnosis.
Interventions
OTHERBlood sample
Sponsors
Central Hospital, Nancy, France
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with certain etiologic diagnosis established with NGS | day 0 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Percentage of patients with etiologic diagnosis established with NGS or with other techniques (array-CGH) | 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 |
| CNVs detected with NGS or array-CGH (reference technique for CNV detection). | day 0 |
Countries
France
Outcome results
None listed