Genetic and Epigenetic Variations in Heterokaryotypic Monozygotic Twins Discordant for Down Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Study of epigenetic modifications
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 11 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- 未提供
结局指标
主要结局
Study of epigenetic modifications
时间窗: 1 year
DNA methylation pattern
Identification of active genes
时间窗: 1 year
Analysis of transcriptomic profile from RNA samples
Analysis of the coding and non-coding genetic variations between participants
时间窗: 1 year
Whole Genome Sequencing of DNA samples
Identification of the proteins regulated differently
时间窗: 1 year
Analysis of proteomic profile from plasma samples
Link specific proteins to some specific complications seen in patients with Down syndrome
时间窗: 1 year
Analysis of proteomic profile from plasma samples
Determination of the mechanisms of genes regulation
时间窗: 1 year
Analysis of transcriptomic profile from RNA samples
Definition of the network of genes expression
时间窗: 1 year
Analysis of transcriptomic profile from RNA samples
次要结局
未报告次要终点