Transcriptomic Analysis (RNAseq) of Blood and Fibroblasts to Establish a Diagnosis in Patients With Rare Diseases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- Patients with identified deleterious variant at RNA level
研究概览
简要总结
This study aims to answer a key question in the field of rare genetic diseases by determining the prevalence of deleterious variants at RNA level in undiagnosed patients with intellectual disability and/or neonatal hypotonia. This study will put an end to diagnostic erraticism in a number of patients.
Finally, the results of this study will make it possible to compare the two types of tissue used for RNAseq, with a view to facilitating the implementation of this analysis method in the diagnostic setting.
详细描述
Rationale:
The majority of patients with intellectual disability or neonatal hypotonia remain undiagnosed, despite extensive genetic testing. In fact, standard analyses aimed at detecting abnormalities in the patient's DNA only enable a diagnosis to be made in a third of cases. Our hypothesis is that a certain number of these misdiagnosed patients carry anomalies (pathogenic variants) disrupting the RNA (transcript), which were not identified by DNA sequencing.
This study aims to answer a key question in the field of rare genetic diseases by determining the prevalence of deleterious variants at RNA level in undiagnosed patients with intellectual disability and/or neonatal hypotonia. This study will put an end to diagnostic erraticism in a number of patients.
Finally, the results of this study will make it possible to compare the two types of tissue used for RNAseq, with a view to facilitating the implementation of this analysis method in the diagnostic setting.
Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 0-99 years
- •Patient with neonatal intellectual disability and/or hypotonia followed at one of three inclusion centers
- •Patient or parent has been informed about the study and has signed an informed consent form
- •Genetic analysis by high-throughput DNA sequencing (gene panel, exome, genome) did not identify any abnormality explaining the patient's phenotype.
- •If the patient's phenotype is suggestive of Prader-Willi syndrome or Angelman syndrome: a methylation anomaly test on chromosome 15 was negative.
- •If the patient's phenotype is suggestive of fragile X syndrome: a repeat expansion analysis of the FMR1 gene was negative.
- •If the patient's phenotype is suggestive of myotonic dystrophy type I, DM1: a repeat expansion analysis of the DMPK gene was negative.
- •Patient entitled to or beneficiary of a social security scheme
排除标准
- •Patient deprived of liberty
- •Pregnant or breast-feeding woman,
- •The person required to sign the consent form does not understand French
- •Person under guardianship and/or curatorship
研究组 & 干预措施
ARNseq
Patients enrolled in the experimental arm will be seen in consultation to sign the consent form and take samples at one of the participating investigational sites.
Only one visit is planned as part of the study. This is the inclusion visit, during which skin and blood samples are taken.
If a pathogenic variant explaining the phenotype is identified in a patient, the clinician following the patient will request confirmation of the variant by targeted analysis (Sanger sequencing) as part of the diagnosis. This result will be returned by the clinician who follows the patient as part of his or her usual care.
干预措施: Blood collection (Procedure)
ARNseq
Patients enrolled in the experimental arm will be seen in consultation to sign the consent form and take samples at one of the participating investigational sites.
Only one visit is planned as part of the study. This is the inclusion visit, during which skin and blood samples are taken.
If a pathogenic variant explaining the phenotype is identified in a patient, the clinician following the patient will request confirmation of the variant by targeted analysis (Sanger sequencing) as part of the diagnosis. This result will be returned by the clinician who follows the patient as part of his or her usual care.
干预措施: skin biopsy (Procedure)
结局指标
主要结局
Patients with identified deleterious variant at RNA level
时间窗: Through study completion, an average of 42 month.
The number of patients initially in diagnostic errancy in whom a deleterious variant at RNA level was identified by transcriptomic analysis (RNAseq).
次要结局
- Comparison of the number of variants obtained from blood and from fibroblasts(Through study completion, an average of 42 month.)