Hanson Britt, Paternoster Ben, Povarnitsyn Nikita, Scotchman Elizabeth, Chitty Lyn, Chandler Natalie
North Thames Genomic Laboratory Hub, Great Ormond Street NHS Foundation Trust, London WC1N 3BH, UK.
Genetic and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Extracell Vesicles Circ Nucl Acids. 2023 Feb 22;4(1):3-26. doi: 10.20517/evcna.2022.44. eCollection 2023.
Prenatal testing is important for the early detection and diagnosis of rare genetic conditions with life-changing implications for the patient and their family. Gaining access to the fetal genotype can be achieved using gold-standard invasive sampling methods, such as amniocentesis and chorionic villus sampling, but these carry a small risk of miscarriage. Non-invasive prenatal diagnosis (NIPD) for select rare monogenic conditions has been in clinical service in England since 2012 and has revolutionised the field of prenatal diagnostics by reducing the number of women undergoing invasive sampling procedures. Fetal-derived genomic material is present in a highly fragmented form amongst the maternal cell-free DNA (cfDNA) in circulation, with sequence coverage across the entire fetal genome. Cell-free fetal DNA (cffDNA) is the foundation for NIPD, and several technologies have been clinically implemented for the detection of paternally inherited and pathogenic variants. Conversely, a low abundance of cffDNA within a high background of maternal cfDNA makes assigning maternally inherited variants to the fetal fraction a significantly more challenging task. Research is ongoing to expand available tests for maternal inheritance to include a broader range of monogenic conditions, as well as to uncover novel diagnostic avenues. This review covers the scope of technologies currently clinically available for NIPD of monogenic conditions and those still in the research pipeline towards implementation in the future.
产前检测对于罕见遗传病的早期发现和诊断至关重要，这些疾病会给患者及其家庭带来改变生活的影响。获取胎儿基因型可通过金标准侵入性采样方法实现，如羊膜穿刺术和绒毛取样，但这些方法存在小流产风险。自2012年以来，针对特定罕见单基因疾病的非侵入性产前诊断（NIPD）已在英国投入临床应用，通过减少接受侵入性采样程序的女性数量，彻底改变了产前诊断领域。胎儿来源的基因组物质以高度碎片化的形式存在于循环中的母体游离DNA（cfDNA）中，覆盖整个胎儿基因组的序列。游离胎儿DNA（cffDNA）是NIPD的基础，已有多种技术在临床上用于检测父系遗传和致病变异。相反，在母体cfDNA的高背景下，cffDNA丰度较低，这使得将母系遗传变异分配到胎儿部分成为一项更具挑战性的任务。目前正在进行研究，以扩大针对母系遗传的可用检测范围，涵盖更广泛的单基因疾病，并探索新的诊断途径。本综述涵盖了目前临床上可用于单基因疾病NIPD的技术范围，以及那些仍处于研究阶段、未来有望实现临床应用的技术。
