Various Type of Genetic Events in Patients With Intellectual Disability (CNV-Seq)

Evaluation of Tools for the Simultaneous Detection of Point and Structural Mutations in Patients With Intellectual Disability

Currently, for a patient with intellectual disability without a recognizable syndrome (most cases), the way to diagnosis is often long, tedious and expensive because different approaches are used one after the other to identify structural variants (duplications, deletions and other) and point mutations (sequencing of one or more candidate genes). The development of high-throughput sequencing techniques (next generation sequencing: NGS) has drastically increased the detection of point mutations offering the possibility to test a large number of genes simultaneously. NGS also shows a huge potential in detecting structural variants. The objective of this research is to assess the sensitivity of a simultaneous detection of point mutations and structural variants by NGS approaches. This would bring together in a single step the equivalent of performing an array-Comparative genomic hybridization (CGH) analysis plus performing a targeted sequencing of candidate genes. Investigators will compare two approaches for this simultaneous detection: a targeted enrichment of candidate genes coding regions using probes covering these regions associated with a backbone of genomic probes, an approach that could be implemented immediately in diagnostic at the hospital, and a whole genome sequencing (WGS), that is currently a too expensive tool for routine diagnosis but that should be the approach used in the future. Investigators will compare these two approaches to the traditional one: CGH array + WGS. The implementation of a "one step" strategy to detect both types of mutations (punctual and structural) would accelerate and improve the access of patients to a molecular diagnosis.

Study Overview

• Status: Unknown
• Conditions: Intellectual Disability
• Intervention / Treatment: Genetic: Blood samples

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients with intellectual deficit without diagnosis

Description

Inclusion Criteria:

• Patients with developmental disabilities
• No etiologic diagnosis but suspected genetic cause
• Fragile X syndrome research negative

Exclusion Criteria:

• Children born to consanguineous couples
• Diagnosis already established or suspected
• Identification of an independent etiology

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Detection of mutation from the CGH-array technology on 475 genes	One year

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 23, 2016
• First Posted (Estimate): August 26, 2016

Study Record Updates

• Last Update Posted (Estimate): August 26, 2016
• Last Update Submitted That Met QC Criteria: August 23, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Intellectual Disability
• Other Study ID Numbers: 6374

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO