NCT04564235已完成不适用
Risk of Recurrence of de Novo Mutations: Research and Quantification of Paternal Germinal Mosaicism by the Combined Use of Genomic Tools
University Hospital, Rouen1 个研究点 分布在 1 个国家目标入组 5 人开始时间: 2021年2月24日最近更新:
适应症
干预措施
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Proportion of the patient's de novo mutations detectable in the father's sperm
研究概览
简要总结
- Inclusion of 5 families Inclusions will be made by the clinical genetics department of the Rouen University Hospital (monocentric study) and will correspond to trios of parents + child with unexplained developmental abnormalities. The inclusion of patients will be integrated in routine care and will have as immediate benefit for the included families the extensive analysis of the proband and their parents' genomes by short and long read sequencing techniques, which represent the most comprehensive diagnostic tests for developmental diseases, and which are not currently routinely available. Inclusion in clinical genetics by clinicians accustomed to prescribing genome-wide analyses will allow clear and complete information to families. Collection of consents. The trio's DNA will already be available at the molecular genetics laboratory, and a new blood sample may be proposed if necessary. Collection of sperm from the father.
- Identification of a large set of de novo mutations. Extraction of blood DNA and sending for sequencing of the complete genome to the National Centre for Research in Human Genomics (CNRGH, Evry), in the framework of a collaboration already initiated. Analysis of the sequencing data thanks to the already existing expertise in Rouen. Identification of about 40-120 de novo mutations per trio. At this stage: interpretation of the variations identified with the secondary objective of identifying the cause of the disease in children. Long read genomes will allow to phase the de novo variants to the paternal or to the maternal haplotype.
- Search for de novo mutations in paternal sperm samples. Extraction of spermatic DNA. Design of a sequencing panel targeting the genetic variations identified in the different trios. Preparation of the libraries, targeted high throughput sequencing at great depth thanks to the techniques and equipment already operational. Specific search for the de novo variations identified in the probands (in 2.), with for each evaluation of (i) the presence of the variation in the sperm sample, (ii) the quantity of mosaicism, reflecting the proportion of carrier spermatozoa and therefore the risk of recurrence, (iii) the presence of my variation in the blood sample of both parents in deep sequencing.
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
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Trio consisting of a child with a developmental disorder and both unaffected parents
- •Absence of etiology after clinical expertise and genetic testing
- •Indication of a genome-wide sequencing analysis
- •Child from spontaneous pregnancy without ovulation stimulation treatment
- •Availability of DNA blood samples
- •Affiliation to a social insurance
- •Patient or patient's legal representative who has read and understood the information letter and has signed the consent form
排除标准
- •Lack of indication for a genome-wide analysis in the proband
- •Etiology of the developmental disorder already identified
- •Proband born after In-Vitro Fertilization
- •Impossibility of non-invasive sperm collection from the father
研究组 & 干预措施
Indication for a genome-wide analysis in the proband
Experimental
干预措施: genome-wide analyses (Genetic)
Indication for a genome-wide analysis in the proband
Experimental
干预措施: Search for de novo mutations in paternal sperm samples (Genetic)
结局指标
主要结局
Proportion of the patient's de novo mutations detectable in the father's sperm
时间窗: Day 1
次要结局
- Number of patients for whom molecular diagnosis has been obtained (cause of developmental disability identified) ≥1(Day 1)
研究者
研究点 (1)
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