Universal Haplotype-Based Non Invasive Prenatal Diagnosis by Linked-Read Sequencing (10XGenomics™ Technology)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 11
- 主要终点
- Non-invasive Prenatal Diagnosis of Monogenic Disorders
研究概览
简要总结
Description of the presence of cell-free fetal DNA in maternal plasma allowed the possibility of non-invasive prenatal diagnosis. Whereas detection of paternally-inherited alleles is straightforward and being quickly implemented in routine, detection of maternally-inherited alleles remains challenging.
To date, the main approach that is being developped, called Relative Haplotype Dosage Analysis, relies on the identification of an allelic imbalance between the mother's wild-type and mutant alleles, relative to the fetal's contribution. This approach therefore requires the study of a propositus to identify the morbid haplotype, which is not always possible in the context of an ongoing pregnancy.
In this study, we aim to evaluate the contribution of new technologies, such as linked-read Sequencing, to allow direct identification of parental haplotype in the context of non-invasive prenatal diagnosis.
详细描述
Objectives:
The description of cell-free fetal DNA in maternal plasma offered the possibility of a non invasive approach for prenatal diagnosis (Non Invasive Prenatal Diagnosis, NIPD). However, only a small fraction of total cell-free DNA is of fetal origin, and its study widened only recently with the development of new technologies, such as digital PCR and Massively Parallel Sequencing.
Circulating fetal cells (CFC) represent a promising approach, but need further development before routine implementation To date, clinical applications are limited to Non Invasive Prenatal Testing for fetal aneuploidy and non invasive detection of fetal-specific genomic regions, for example fetal sex determination or fetal RHD genotyping, or more recently de novo mutations that can be suspected after echographic findings, such as achondroplasia. Yet, NIPD of maternally-inherited monogenic diseases remains challenging, for the fetal allele is hidden within a large amount of identical maternal sequences. Some publications report successful NIPD of maternally-inherited monogenic diseases, but only on case reports or small cohorts, without a standardized protocol and control of statistical risks.
In this study, we aim :
- to develop a new non invasive approach to Prenatal Diagnosis using both direct and indirect strategy by Massively Parallel Sequencing,
- to identify and characterize CFC.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Pregnancies at 25% risk of being affected by Cystic Fibrosis with previously identified pathogenic variants
- •Couple asking for invasive prenatal diagnosis
- •Pregnancy at 8 weeks of gestation or later
排除标准
- •Couple not asking for prenatal diagnosis
- •No signed consent obtained
结局指标
主要结局
Non-invasive Prenatal Diagnosis of Monogenic Disorders
时间窗: 3 years
Development of a robust and standardized NIPD protocol relying on Relative Haplotype Dosage Analysis after deciphering of parental haplotype by Linked-Read Sequencing
次要结局
- Description of Circulating Fetal Cells(3 years)