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Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11.2 Microdeletional Syndrom (CSRK05)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04141540
Recruitment Status : Not yet recruiting
First Posted : October 28, 2019
Last Update Posted : January 7, 2020
Information provided by (Responsible Party):
Hôpital le Vinatier

Brief Summary:
The 22q11.2 microdeletion syndrome (22q11.2DS) is a rare disease with a psychiatric phenotype. Indeed, the diagnosis of schizophrenia is made in 5 to 10% of adolescents and 25 to 40% of adults carrying the 22q11DS. Thus, although this pathology has been able to provide a genetically homogeneous model for the study psychosis etiology, it is not currently possible to establish a link between genomic rearrangement and psychotic symptoms. However, this robust model of genetic vulnerability could provide us a lot of translational informations about schizophrenia genetics. To go furthermore, twin studies have provided us precious data for the study of hereditary diseases. Combining this two approaches, the translational 22q11.2 project proposes a molecular study of two monozygotic 22q11.2DS twins discordant for the psychiatric phenotype -one carrying schizophrenia and the other having no psychiatric symptoms-.

Condition or disease Intervention/treatment Phase
Di George Syndrome Genetic: Molecular analyses Not Applicable

Detailed Description:
The main objective of the study is to propose a whole exome sequencing (WES), pan-genomic in whole genome sequencing (WGS), transcriptomic, epigenomic and intestinal microbiome approaches in order to determine specific molecular basis of psychotic symptoms in 22q11.2DS.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: It's a study with a comparative monocentric cross-sectional analysis model.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Translational 22q11.2:"Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11.2 Microdeletional Syndrom"
Estimated Study Start Date : January 25, 2020
Estimated Primary Completion Date : February 15, 2020
Estimated Study Completion Date : March 31, 2020

Arm Intervention/treatment
Groupe "Twin 1"
Twin 1 with psychotic symptoms (PANSS +) Molecular analyses 1
Genetic: Molecular analyses
Comparaison of the molecular profil between two monozygotic twins carrying a deletion 22q11.2

Groupe "Twin 2"
Twin 2 without psychotic symptoms (PANSS +) Molecular analyses 2
Genetic: Molecular analyses
Comparaison of the molecular profil between two monozygotic twins carrying a deletion 22q11.2

Primary Outcome Measures :
  1. Whole exome sequencing [ Time Frame: 6 months ]
    Searching for mosaic genetic variations that may have occurred secondarily to conception

Secondary Outcome Measures :
  1. Transcriptome [ Time Frame: 6 months ]
    two methods of mRNA extraction will be used: from the establishment of lymphoblastoid lines and from whole blood collected on paxgene® tube. After depletion of ribosomal RNA, the RNAs will be converted into complementary DNAs and libraries will be made using 100 to 200ng of total RNA. Libraries will be sequenced in a paired-end to generate 80 million reads per sample. The data will be analyzed with the HTSeq suite to count the number of reads associated with each gene annotated in the latest version of the genome. The DESeq bioconductor suite will be used to normalize the expression. A study to identify differentially expressed genes will be performed with this tool and GFold. Genes showing statistically significant differential expression will be validated by RT-qPCR

  2. Methylome [ Time Frame: 6 months ]
    This analysis will be carried out in collaboration with " L'hôpital de Sainte Anne2 (Inserm UMR_S894 "Physiology of psychiatric diseases" - Professor Marie-Odile KREBS). The DNA will be extracted from whole blood collected on paxgene® tube. The methylation of the entire genome of twin siblings will be studied by the Infinium MethylationEPIC BeadChip chip (Illumina) that covers 850,000 CpG and the set of genes after bisulfite DNA processing. The statistical analysis of the methylation differences will be carried out with the R software (minfi and ChAMP packages) in order to highlight the DMP (Differentially Methylated Probes) as well as the DMR (Differentially Methylated Regions, probes contigues).

  3. Microbiotic DNA [ Time Frame: 6 months ]
    A quantitative metagenomic analysis will be carried out on the basis of a sequencing of the genetic material extracted from the intestinal microbiome in the stools of the two twins

  4. Positive And Negative Syndrome Scale (PANSS) [ Time Frame: 6 months ]
    Scale of evaluation of positive and negative syndromes of schizophrenic symptomatology.The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers.As 1 rather than 0 is given as the lowest score for each item, a patient can not score lower than 30 for the total PANSS score. Scores are often given separately for the positive items, negative items, and general psychopathology.

  5. Mini-International Neuropsychiatric Interview (MINI) [ Time Frame: 6 months ]
    The modalities for answering all the Mini-International Neuropsychiatric Interview (MINI)questions are "YES" or "NO". If the answers to these filter questions are positive, the following ones are asked allowing to validate or invalidate the diagnosis concerned.

  6. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 6 months ]
    The Hospital Anxiety and Depression Scale (HADS) is an instrument for detecting anxiety and depressive disorders. It has 14 listed items from 0 to 3. Seven questions relate to anxiety (total A) and seven others to the depressive dimension (total D), allowing thus obtaining two scores (maximum score of each score = 21).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • • Sisterhood of monozygotic twins diagnosed with de novo 22q11.2DS is confirmed by CGH array and discordant for the psychiatric phenotype

Exclusion Criteria:

  • • Refusal to use data for research purposes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04141540

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Contact: DEMILY CAROLINE, M.D., Ph.D 0033437915163
Contact: VIAL VERONIQUE 0033437915531

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Hopital Vinatier
Lyon, Rhone Alpes, France, 69678
Sponsors and Collaborators
Hôpital le Vinatier
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Principal Investigator: DEMILY CAROLINE, MD PH.D Centre Hospitalier le Vinatier & CNRS UMR 5229 (BRON, France)

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Responsible Party: Hôpital le Vinatier Identifier: NCT04141540    
Other Study ID Numbers: 2019-A00852-55
First Posted: October 28, 2019    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hôpital le Vinatier:
22q11.2 Microdeletional
Additional relevant MeSH terms:
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DiGeorge Syndrome
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
22q11 Deletion Syndrome
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Lymphatic Abnormalities
Lymphatic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Parathyroid Diseases
Endocrine System Diseases