Targeted Next Generation Sequencing and Intellectual Disability

Completed

• Conditions: Intellectual Disability
• Interventions: Other: Blood sample

• Registration Number: NCT02889068
• Lead Sponsor: Central Hospital, Nancy, France

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2016-08-31
• Study First Submitted QC: 2016-08-31
• Study First Posted: 2016-09-05
• Primary Completion: 2016-09-30
• Study Completion: 2017-01-30
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-27
• Last Update Posted: 2017-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intellectual disability	Blood sample	-

Primary Outcome Measures

Name	Time	Method
Percentage of patients with certain etiologic diagnosis established with NGS	day 0

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Chru Nancy; 🇫🇷 Vandœuvre-lès-Nancy, France