Clinical trial NCT05767216: Genetic and Epigenetic Variations in Heterokaryotypic Monozygotic Twins Discordant for Down Syndrome
Official title: Genetic and Epigenetic Variations in Heterokaryotypic Monozygotic Twins Discordant for Down Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Down Syndrome
Lead sponsor: Institut Jerome Lejeune
Sponsor class: OTHER
First posted: 2023-03-14
Enrollment: 5
Sex: MALE
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Analysis of the coding and non-coding genetic variations between participants
timeFrame: 1 year
measure: Study of epigenetic modifications
timeFrame: 1 year
measure: Identification of active genes
timeFrame: 1 year
measure: Determination of the mechanisms of genes regulation
timeFrame: 1 year
measure: Definition of the network of genes expression
timeFrame: 1 year
measure: Identification of the proteins regulated differently
timeFrame: 1 year
measure: Link specific proteins to some specific complications seen in patients with Down syndrome
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut Jérôme Lejeune
Study officials:
References: