Clinical trial: Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic (NCT02136849)

Eligibility criteria:
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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.



Patient description (medical language): A 15-year-old boy with mild intellectual disability is brought to the office by his parents for a routine physical examination.  The boy is going to a school for students with learning disabilities.  The patient was adopted, and his immunizations are up to date.  Review of the patient's medical records is notable for cytogenetic studies that showed a small gap near the tip of the long arm of the X chromosome, which is consistent with fragile X syndrome, an X-linked disorder. The defect is an unstable expansion of trinucleotide repeats (CGG) in the fragile X mental retardation 1 (FMR1) gene, located on the long arm of the X chromosome. He is not using any medications and vital signs are within normal levels. His blood chemistry analysis as bellow:
Blood Chemistry Value      Normal Range     Patient Value
Glucose                    90-120 mg/dl     95 mg/dl
BUN (Blood Urea Nitrogen)  7-24 mg/dl       10 mg/dl
Creatinine                 0.7-1.4 mg/dl    0.8 mg/dl
Calcium                    8.5-10.5 mg/dl   9 mg/dl
Sodium                     134-143 mEq/L    135 mEq/L
Potassium                  3.5-4.5 mEq/L    3.7 mEq/L
Chloride                   95-108 mEq/L     98 mEq/L
CO2                        20-30 mEq/L      25 mEq/L
Blood pH                   7.38-7.42        7. 39

Patient description (patient's own words): My husband and I brought our 15-year-old son to the clinic for his routine exam. My son is going to school for special needs students. We adopted him a few years ago. His vaccinations are up to date. He already passed some chromosome testing and they found that he has a fragile X syndrome. The doctor told us that it comes from repeats in the fragile X chromosome. My son is not using any medication and his blood pressure temperature and breathing were normal during the exam. He also did a blood test. The results came back and showed that his blood sugar urea creatinine calcium sodium potassium chloride CO2 and blood pH were all within the normal range.

Does the patient match the trial criteria? Contradiction