Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic

Nantes University Hospital5 个研究点分布在 1 个国家目标入组 228 人2014年9月

适应症Severe Intellectual Disability

概览

阶段: 不适用
干预措施: 未指定
疾病 / 适应症: Severe Intellectual Disability
发起方: Nantes University Hospital
入组人数: 228
试验地点: 5
主要终点: Number of patients for which a mutation responsible for the de novo patients DI has been identified
状态: 已完成
最后更新: 7年前

概览研究者入排标准结局指标研究点相似试验

概览

简要总结

Intellectual disability (ID) moderate or severe affects about one child in 250, with 3000 to 4000 new cases each year. Chromosomal or molecular pathology causes are not identified in half of the cases by current techniques. Studies show that de novo mutations are common in many different genes. The "exome" approach by high-throughput sequencing (NGS) has emerged as the technique of choice for identifying and comparing the exome of the child to the parent. We wish to evaluate this approach and its contribution in the diagnostic management of 50 patients with DI seen in genetics in 6 CHU Great West. Genomics platform IBISA / Biogenouest will provide technological and bioinformatics support this project.

注册库

clinicaltrials.gov

开始日期

2014年9月

结束日期

2016年1月

最后更新

7年前

研究类型

Observational

性别

All

研究者

发起方

Nantes University Hospital

责任方

Sponsor

入排标准

入选标准

•Patients with severe intellectual disability (IQ \<35 ) or moderate (IQ \<50) isolated or syndromic presentation but undiagnosed . The diagnosis is established during genetic counseling of a 6 CHU interregion
•Lack of family history ( parents). We are interested in this project to patients who do not have family history in order to increase the probability of identifying a de novo mutation . We do not however exclude the hypothesis for some patients a mechanism recessive autosomal or X-linked .
•Recruitment in 6 CHU HUGO . Patients are required to have been seen in genetics in a 6 CHU interregion . Molecular analyzes of the Fragile X syndrome and the CGH technique must be negative.
•Indication sequencing exomique adopted by the Scientific Committee. The Scientific Committee HUGODIMS project role to select patients whose DNA will be studied in order to optimize the chances of success for sequencing . This selection must take into account clinical parameters , but also genetic parameters ( potential inbreeding ) . The files will be selected by videoconferencing at the end of the monthly meeting of CLAD . The methodologist of the study will be invited to videoconferencing.
•specific consent obtained for the study.

排除标准

•Parents patient with moderate or severe intellectual disability disagree with the preferred hypothesis of de novo mutation or recessive transmission mechanism.
•Form with known syndromic diagnosis can be targeted molecular studies (clinical signs).
•Cause molecular DI identified by targeted molecular analysis or CGH.
•Explicit refusal to participate in the study of the patient, parents, or one of the two parents.
•Any other indication that intellectual disability.
•The parents of the patient or the patient may be removed.

结局指标

主要结局

Number of patients for which a mutation responsible for the de novo patients DI has been identified

时间窗: 18 months

次要结局

Number of de novo mutations (loss of function, missense or indels) probably pathogens identified are not known to be involved in the DI genes.(18 months)
Number of patients for whom the study of exomes revealed mutations in genes compatible with the mode of recessive autosomal recessive or X-linked chromosome(18 months)