Search of Susceptibility Genes in Autism Spectrum Disorders
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,616
- 试验地点
- 9
- 主要终点
- Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder
研究概览
简要总结
The main objective of the study is to define, for Autism Spectrum Disorder, the extent of genetic variation in synaptic pathways that may be targeted for therapeutic development. For this purpose the investigators will take advantage of large, well-characterized cohorts of patients with Autism Spectrum Disorder for genetic screenings. Targeted sequencing of selected synaptic genes, previously associated with Autism Spectrum Disorder, will be carried out in these cohorts with deep coverage of coding regions and a strong focus on previously untested regulatory regions. Genomic data from Copy Number Variant, whole genome sequencing and exome sequencing, available for some of these patients, will be integrated in the overall analysis. The investigators will strongly emphasize the establishment of comprehensive genotype/phenotype correlations and set up an induced Pluripotent Stem Cells collection from selected patients with synaptic mutations for functional and expression analysis.
详细描述
Specific aims are:
Aim 1: To identify genetic variants in selected synaptic genes, by targeted sequencing with deep coverage of coding regions and a strong focus on previously untested regulatory regions in Autism Spectrum Disorder
Aim 2: To define the range of clinical phenotypes caused by mutations in synaptic genes by establishing detailed genotype/phenotype correlations and analyzing segregation in families with multiple individuals affected by Autism Spectrum Disorder, Autism Spectrum Disorder traits or other neuropsychiatric disorders
Aim 3: To generate a repository of induced Pluripotent Stem Cells from Autism Spectrum Disorder subjects with synaptic mutations for translational studies, including expression and functional assays.
Aim 4: To identify the neuronal phenotypes caused by deleterious synaptic mutations for further translational studies
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Months 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis for Autism Spectrum Disorders or Autism using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria
排除标准
- •Patients with profound intellectual disability or with a known medical cause of autism, such as neurocutaneous syndromes, Fragile X, metabolic disorders, extreme prematurity, congenital rubella and other prenatal or postnatal neurological infections or gross dysmorphology, will be excluded
结局指标
主要结局
Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder
时间窗: up to 12 months after completion of the inclusion and molecular explorations
次要结局
- Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorders:(up to 12 months after completion of the inclusion and molecular explorations))