Clinical trial NCT02889068: Targeted Next Generation Sequencing and Intellectual Disability
Official title: Targeted Next Generation Sequencing and Intellectual Disability
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intellectual Disability
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2016-09-05
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with severe to moderate intellectual disability, with syndrome or not.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients with certain etiologic diagnosis established with NGS
timeFrame: day 0
Secondary outcomes:
measure: Percentage of patients with etiologic diagnosis established with NGS or with other techniques (array-CGH)
timeFrame: day 0
measure: Obtained read depth according to number of pooled samples
timeFrame: day 0
measure: Percentage of patients with variant with unknown significance, needing supplementary analyses to prove its involvement in intellectual disability
timeFrame: day 0
measure: CNVs detected with NGS or array-CGH (reference technique for CNV detection).
timeFrame: day 0
measure: Clinical phenotype for each gene for which a causal mutation is identified by NGS
timeFrame: day 0
measure: Time of analysis of NGS raw data
timeFrame: day 0
Other outcomes:
Locations:
city: Vandœuvre-lès-Nancy
country: France
facility: Chru Nancy
Study officials:
affiliation: CHRU de Nancy Laboratoire de Génétique Hôpitaux de Brabois
name: Céline BONNET
role: PRINCIPAL_INVESTIGATOR
References: