无创胎儿游离DNA检测用于单基因病诊断（科学影响论文第80号）

原文

The DNA code represents a genetic instruction as to how the human body develops and works. A 'spelling mistake' in the DNA code of the developing fetus can lead to a single gene condition. Examples of single-gene conditions include cystic fibrosis, sickle cell disease and Huntington's disease. Single gene conditions collectively affect 1 in 100 births and can be inherited from one or both parents, or can occur without any family history, arising spontaneously out of a one-off change (pathogenic variant) in a known gene. Sometimes there can be specific anomalies seen on the ultrasound scan that suggest this. Autosomal dominant inheritance is where a parent has the spelling mistake in their DNA and there is then a 1 in 2 (50%) chance that the baby will inherit the condition. Alternatively, both parents may be carriers of the spelling mistake within their DNA code but do not themselves have the condition (autosomal recessive inheritance), in which case there is then a 1 in 4 (25%) chance of having a baby with that condition. There are also X-linked (sex-linked) conditions where usually only boys can inherit the condition, while girls can be carriers. Traditionally, when embarking on a pregnancy where there is a risk of a baby being affected with a genetic condition, invasive testing using amniocentesis (via a needle through the mother's abdomen to take a sample of amniotic fluid from around the baby) or chorionic villus sampling (via a needle through the mother's abdomen to take a sample from the placenta) is offered to the parents to obtain a sample of DNA from the baby to test for the condition. However, these tests are invasive involving a needle going into the womb and can carry a small miscarriage risk of around 1 in 200. It is now known that DNA from the placenta (which represents the DNA in the baby) circulates in the mother's blood from early pregnancy. This is known as cell-free fetal DNA (cffDNA) and so is a potential source of genetic material that can be used to test the baby for selected genetic conditions. Discovery of cffDNA in the mother's blood now allows for testing for genetic conditions as early as the 8th week of pregnancy, commonly referred to as non-invasive prenatal diagnosis (NIPD). Its use has evolved in clinical practice from 2011 when it was originally developed to screen for common chromosome differences such as Down, Edwards and Patau syndromes and for this purpose is referred to as non-invasive prenatal screening or testing (NIPS/T). While the acronym of 'NIPD' is similar to 'NIPS/T' it is important to be clear that these test for different things, can be a screening or a diagnostic test and use different technological approaches. The mother's own cell-free DNA (cfDNA) will also be present in the sample and must be distinguished from that of her developing fetus. NIPD is currently available in the UK through the National Health Service (NHS) for some limited scenarios, for example, where parent(s) have already had a baby affected by a condition, or to test for specific conditions where there are differences detected on an ultrasound scan that suggest certain conditions. This testing can be performed on a blood sample taken from the mother any time from 8 weeks of gestation, i.e. earlier than invasive testing and with no risk. If the condition being tested for is already known because of family history, this test is considered diagnostic and no further testing for confirmation is required.