Clinical trial: Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study (NCT02862808)

Eligibility criteria:
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
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? 0