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.

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

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.

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