Genetic and Epigenetic Variations in Heterokaryotypic Monozygotic Twins Discordant for Down Syndrome (Colibri)

Heterokaryotypic monozygotic twins discordant for Down syndrome (DS) are very rare, with an incidence estimated to be less than 1 over 7,000,000 pregnancy in the general population. Sharing the same genetic patrimony, except for an additional chromosome 21 for one of them, any gene-expression difference between them could be attributed only to the supernumerary chromosome 21 and not to polymorphic variability in the rest of the genome. The setting up of a prospective longitudinal study will offer the major advantage of allowing genetic and epigenetic comparisons between them and to obtain important information on the impact of the environment in which they live and grow up.

Study Overview

• Status: Recruiting
• Conditions: Down Syndrome
• Intervention / Treatment: Other: Biological sampling

Detailed Description

It is planned to perform multi-omics analyses in order to reach an integrated understanding of the effect of genomic changes on protein expression, on biochemical posttranslational modifications of the synthetized proteins and on the modulation of some signalling pathways.

This study will also allow the generation of induced Pluripotent Stem Cells (iPSCs) from blood cells and fibroblasts of the monozygotic twins useful as in-vitro models to study the pathogenesis and the pathophysiology of Down syndrome. All this may shed the light on new research approaches in Down syndrome.

At last, the human gut microbiome, referring to the total microbial population in the human gastrointestinal tract, although thought to have its own impact, will also be studied. The microbiome is known to play a crucial role mainly in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and controlling neuropsychiatric behaviour

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie Durand; Phone Number: 0033156586300; Email: sophie.durand@institutlejeune.org

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Institut Jerome Lejeune
    • Contact: Sophie Durand; Phone Number: 0156586300; Email: sophie.durand@institutlejeune.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Twins of a heterokaryotypic monozygotic pair discordant for DS
• Twins of a sex- and class of age-matched dizygotic pair discordant for DS,
• Sex- and class of age-matched patient with mosaic T21
• Subject's parents/legal representatives willing to give written informed consent.
• Subject and his/her parents/legal representatives must be able/willing to comply with the protocol.
• Subject covered by social welfare.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Down syndrome children; Two pairs of twins discordant for Down syndrome and 1 children with mosaic Down syndrome will be recruited. Blood, skin and feces samples will be specifically collected for the purpose of the study.	Other: Biological sampling; Blood, skin and stool samples for laboratory analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of the coding and non-coding genetic variations between participants	Whole Genome Sequencing of DNA samples	1 year
Study of epigenetic modifications	DNA methylation pattern	1 year
Identification of active genes	Analysis of transcriptomic profile from RNA samples	1 year
Determination of the mechanisms of genes regulation	Analysis of transcriptomic profile from RNA samples	1 year
Definition of the network of genes expression	Analysis of transcriptomic profile from RNA samples	1 year
Identification of the proteins regulated differently	Analysis of proteomic profile from plasma samples	1 year
Link specific proteins to some specific complications seen in patients with Down syndrome	Analysis of proteomic profile from plasma samples	1 year

Collaborators and Investigators

• Sponsor: Institut Jerome Lejeune

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2028

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Down Syndrome
• Other Study ID Numbers: Colibri

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No