Genetic and Epigenetic Variations in Heterokaryotypic Monozygotic Twins Discordant for Down Syndrome
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Biological sampling.
- Who it may be relevant to
- Registry conditions: Down Syndrome. Basic parameters: 4 years — 11 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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
Interventions
- Other Biological sampling
Blood, skin and stool samples for laboratory analysis
Primary outcome measures
- Analysis of the coding and non-coding genetic variations between participants [Time frame: 1 year]
- Study of epigenetic modifications [Time frame: 1 year]
- Identification of active genes [Time frame: 1 year]
- Determination of the mechanisms of genes regulation [Time frame: 1 year]
- Definition of the network of genes expression [Time frame: 1 year]
- Identification of the proteins regulated differently [Time frame: 1 year]
- Link specific proteins to some specific complications seen in patients with Down syndrome [Time frame: 1 year]
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
France · 1 center
- Institut Jérôme Lejeune — Paris
Identifiers
NCT: NCT05767216 · Colibri