Clinical Trial: Exploration and Characterization of Genetic and Phenotypic Profile of the"Schizotiste"

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Exploration and Characterization of Genetic and Phenotypic Profile of the "Early Dissociative Disorder" Associated With Autism Spectrum Disorder: a Pilot Study

Brief Summary:

Childhood schizophrenia "early dissociative disorder" is a rare disease with a low incidence of approximately (1 0/00 to 30/00 ). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. As part of the 2011-2013 Interregional hospital Clinical Research program, University Department of Child and Adolescent Psychiatry Pediatric Hospitals of CHU (Centre Hospitalier Universitaire) de Nice Lenval identified 15 patients with a complex phenotype characterized by an early schizophrenia associated with autism spectrum disorders and developmental disabilities in mild to moderate. This phenotype could be a new syndrome called "schizotiste".

The goal of the investigator's project is to define the genetic causes of this phenotype. The technique of high throughput sequencing will be used to obtain the sequence of exomes of these patients and their families. This study will therefore be important to give an accurate diagnosis for patients and their families. Moreover, investigators believe that this project will identify new genes involved allowing a better understanding of the pathophysiology. Recent studies show the involvement of mutations in several genes (eg Shank, NLGN, NRXN and UPF3) in these different clinical phenotypes. However, the genetic basis of the child's schizophrenia are much less well known than those of autism spectrum disorder.


Detailed Summary:

Childhood schizophrenia "early dissociative disorder" is a rare disease with a low incidence of approximately (1 0/00 to 30/00 ). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. As part of the 2011-2013 Interregional hospital Clinical Research program, University Department of Child and Adolescent Psychiatry Pediatric Hospitals of CHU (Centre Hospitalier Universitaire) de Nice Lenval identified 15 patients with a complex phenotype characterized by an early schizophrenia associated with autism spectrum disorders and developmental disabilities in mild to moderate. This phenotype could be a new syndrome called "schizotiste".

The goal of the investigator's project is to define the genetic causes of this phenotype. The technique of high throughput sequencing will be used to obtain the sequence of exomes of these patients and their families.

This study will therefore be important to give an accurate diagnosis for patients and their families. Moreover, investigators believe that this project will identify new genes involved allowing a better understanding of the pathophysiology. Recent studies show the involvement of mutations in several genes (eg Shank, NLGN, NRXN and UPF3) in these different clinical phenotypes. However, the genetic basis of the child's schizophrenia are much less well known than those of autism spectrum disorder.


Sponsor: Fondation Lenval

Current Primary Outcome: karyotype of genetic abnormalities connected to the phenotype " schizotiste " [ Time Frame: inclusion visit ]

The primary endpoint is based on a number of technical genetic analysis of all subjects.

A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions Big.

The pathological nature of these mutations will be stutied on the gene function and reaches its pattern of expression.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Intensity of positive symptoms of schizophrenia [ Time Frame: inclusion visit ]

    Clinical and neurocognitive description of the phenotype of "child schizotistes" by:

    - Evaluation of the intensity of positive symptoms, negative and general psychopathology and subtypes of schizophrenia by positive and negative syndrome scale (PANSS) without by calculating scores of the 3 dimensions of schizophrenia in PANSS: Positive symptoms (7 items of sides 1-7)), negative symptoms (7 items on sides 1 through 7) and general psychopathology (16 sides items in 1 through 7)), based on these scores diagnosis subtype of schizophrenia is established.

  • disorganization by the scale score Difficulty of language and communication [ Time Frame: inclusion visit ]
    Evaluation of the disorganization of the scale score Trouble of Language and Communication A (TLC A).
  • Evaluation of executive and attentional by the verbal fluency test [ Time Frame: inclusion visit ]
    Evaluation of executive and attentional by the verbal fluency test. The response time to the verbal fluency test scores on the Trail Making Test A (TMT A) and TMT B.
  • Evaluation of memory by the working memory test [ Time Frame: inclusion visit ]
    Evaluation of memory by the Trail Making Test A and B (TMT A, TMT B)
  • Clinical evaluation of autistic symptoms by Autism Diagnostic interview R [ Time Frame: inclusion visit ]
    Clinical evaluation of autistic symptoms by Autism Diagnostic interview R (ADI-R)
  • cognitive functioning [ Time Frame: inclusion visit ]
    Evaluation of cognitive functioning by Wechsler Intelligence Scale for Children Scale IV (WISC IV).
  • Conservation of the mutated amino acid [ Time Frame: inclusion visit ]
    A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially to evaluate the conservation during evolution of the mutated amino acid (PhyloP scores);
  • nucleotide variation in the protein sequence (standard karyotype) [ Time Frame: inclusion visit ]
    A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially to evaluate the prediction of the impact of the nucleotide variation in the protein sequence
  • mutation of DNA on the structure of the protein (standard karyotype) [ Time Frame: inclusion visit ]
    A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially to evaluate the prediction of the impact of the mutation on the structure of the protein


Original Secondary Outcome: Same as current

Information By: Fondation Lenval

Dates:
Date Received: July 29, 2015
Date Started: April 2014
Date Completion: April 2016
Last Updated: September 29, 2015
Last Verified: September 2015