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

Down Syndrome Clinical Trial

— Colibri  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05767216
• Other study ID #: Colibri
• Status: Recruiting
• Phase: N/A
• Start date: December 20, 2022
• Est. completion date: December 30, 2028

Study information

• Verified date: March 2023
• Source: Institut Jerome Lejeune
• Contact: Sophie Durand
• Phone: 0033156586300
• Email: sophie.durand[@]institutlejeune.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: December 30, 2028
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 4 Years to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Down Syndrome
• Syndrome

Intervention

Other:
• Biological sampling
Blood, skin and stool samples for laboratory analysis

Locations

Country	Name	City	State
France	Institut Jérôme Lejeune	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut Jerome Lejeune

Country where clinical trial is conducted

France, 

Outcome

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