NON-INVASIVE PRENATAL TESTING (NIPT) OF FETAL SINGLE-GENE DISORDERS IN MATERNAL BLOOD
试验速览
- 阶段
- 不适用
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Development of a targeted molecular test (mostly standard PCR or real-time PCR) for non-invasive prenatal testing of single-gene disorders.
研究概览
简要总结
Developing a new non-invasive prenatal test for single gene disorders from cell free fetal DNA, retrieved from the mothers blood.
详细描述
Rationale: Conventional prenatal diagnosis (PND) for single-gene disorders requires invasive procedures, either chorionic villus sampling between 11 and 14 weeks gestation or amniocentesis after 15 weeks. Although these approaches to obtain foetal DNA currently provide the golden standard for PND, the invasive procedures carry a risk of miscarriage of 0.5-1%. A reliable non-invasive alternative has long been sought. Circulating cell-free foetal (cff) nucleic acids (DNA and RNA), which are present in maternal blood during pregnancy, can be used for non-invasive prenatal testing (NIPT). NIPT for some chromosomal anomalies (trisomy 21, 13, 18) is now validated. NIPT for other chromosomal anomalies is still under development. NIPT of single-gene disorders is technically very challenging, due to the predominance of maternal DNA sequences, Some small studies have shown that a very limited number of monogenic genetic disorders can currently be diagnosed in maternal blood. In general de novo mutations in the foetus and paternally transmitted disorders are less difficult to diagnose than maternally transmitted disorders.
In this study, the investigators aim to develop non-invasive targeted molecular analysis using cell free fetal (cff) DNA and cff RNA for single-gene disorders, in pregnant women referred to the departments of Clinical Genetics of Maastricht University Medical Centre (MUMC+) and Radboud University Medical Centre (RUMC) for conventional PND. The investigators will contribute to literature by confirming earlier published results, and by adding other single-gene disorders or mutations to the list of disorders for which the possibility of the use of cff DNA will be examined.
Objective: Developing targeted non-invasive prenatal analysis for single-gene disorders using cff DNA and RNA in maternal plasma.
Study design: This study is a proof of concept study in which we aim to demonstrate that molecular analysis can indicate the presence or absence of (a) mutant allele(s) in maternal plasma.
Study population: Pregnant women (≥18y) referred to the Department of Clinical Genetics of MUMC+ or RadboudUMC for conventional PND, for one of the following reasons:
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •the pregnant woman is scheduled for or has recently undergone invasive prenatal testing (regular care) because of one of the following reasons:
- •the fetus is at high risk of a having inherited a single-gene disorder from his/her affected parent(s).
- •the fetus is at risk of having a de dominant novo disorder on the basis of ultrasonography findings.
- •the pregnant woman is 18 years or older
- •the pregnant woman has sufficient understanding of Dutch language and is able to give informed consent
排除标准
- •if in the opinion of the treating physician psychological distress is so severe that asking for participation is not safe
- •the pregnant woman is treated for a malignancy
结局指标
主要结局
Development of a targeted molecular test (mostly standard PCR or real-time PCR) for non-invasive prenatal testing of single-gene disorders.
时间窗: 2014-2016
Main aims are to 1. demonstrate the presence or absence of (a) mutant allele(s) in maternal plasma 2. examine if there is a sufficient concentration of fetal nucleic acids in the maternal plasma to reliably diagnose the monogenic disorder
次要结局
未报告次要终点