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.