Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study

Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study

Evaluation of diagnostic whole exome sequencing in patients with syndromic or isolated severe intellectual disability without a molecular diagnostic, with suspected autosomal recessive inheritance, allowing accurate genetic counseling in this high risk of recurrence group of diseases

Inclusion Criteria:

• Clinical diagnosis of syndromic or isolated severe intellectual disability (IQ <50) without a molecular diagnosis
• Recurrence in siblings (multiplex families) suggesting autosomal recessive inheritance (with or without parental consanguinity) or sporadic cases from a consanguineous union
• Conventional genetic tests performed (including array-CGH) and MRI/CT-scan available
• DNA samples from parents and from both unaffected or affected siblings available, for parental segregation and confirmation of candidate variations identified.
• Availability of a signed informed consent
• To be affiliated or beneficiary of French social security/healthcare system

Exclusion Criteria:

• Parents in the exclusion period of another study or as provided by the national register of volunteers
• High-probability diagnostic hypothesis for which a molecular test is available at lower cost than exome sequencing