Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
Intellectual disability (ID) moderate or severe affects about one child in 250, with 3000 to
 4000 new cases each year. Chromosomal or molecular pathology causes are not identified in
 half of the cases by current techniques. Studies show that de novo mutations are common in
 many different genes. The "exome" approach by high-throughput sequencing (NGS) has emerged as
 the technique of choice for identifying and comparing the exome of the child to the parent.
 We wish to evaluate this approach and its contribution in the diagnostic management of 50
 patients with DI seen in genetics in 6 CHU Great West. Genomics platform IBISA / Biogenouest
 will provide technological and bioinformatics support this project.
Inclusion Criteria:

 -  Patients with severe intellectual disability (IQ <35 ) or moderate (IQ <50) isolated
 or syndromic presentation but undiagnosed . The diagnosis is established during
 genetic counseling of a 6 CHU interregion

 -  Lack of family history ( parents). We are interested in this project to patients who
 do not have family history in order to increase the probability of identifying a de
 novo mutation . We do not however exclude the hypothesis for some patients a mechanism
 recessive autosomal or X-linked .

 -  Recruitment in 6 CHU HUGO . Patients are required to have been seen in genetics in a 6
 CHU interregion . Molecular analyzes of the Fragile X syndrome and the CGH technique
 must be negative.

 -  Indication sequencing exomique adopted by the Scientific Committee. The Scientific
 Committee HUGODIMS project role to select patients whose DNA will be studied in order
 to optimize the chances of success for sequencing . This selection must take into
 account clinical parameters , but also genetic parameters ( potential inbreeding ) .
 The files will be selected by videoconferencing at the end of the monthly meeting of
 CLAD . The methodologist of the study will be invited to videoconferencing.

 -  specific consent obtained for the study.

 Exclusion Criteria:

 -  Parents patient with moderate or severe intellectual disability disagree with the
 preferred hypothesis of de novo mutation or recessive transmission mechanism.

 -  Form with known syndromic diagnosis can be targeted molecular studies (clinical
 signs).

 -  Cause molecular DI identified by targeted molecular analysis or CGH.

 -  Explicit refusal to participate in the study of the patient, parents, or one of the
 two parents.

 -  Any other indication that intellectual disability.

 -  The parents of the patient or the patient may be removed.