Amniotic fluid test for developmental disorders

Genetic studies have revealed surprising links between genes and disease. Most diseases thought to be lifestyle-related are linked to genetic mutations.

The cause of developmental disorders is still unclear, but many related genes have been identified. Our developmental disorder panel test can detect genetic mutations associated with these conditions in amniotic fluid before birth.

Lifestyle diseases such as hypertension (high blood pressure) and type 2 diabetes were thought to be caused by individual lifestyles and habits. However, many genes associated with such diseases have been identified through genome-wide association studies (GWAS).

As a result, we cannot simply classify diseases as caused by lifestyle or genetic mutations. Instead, all diseases are thought to be caused by the interaction of lifestyle, environmental factors, and multiple genes. However, the degree to which the factors contribute varies, and some diseases are considered to be caused by lifestyle or the environment, while others are considered to be caused by genetic mutations.

The causes of developmental disorders are not fully understood. However, it is thought that the cause lies in an innate impairment of brain function rather than inadequate parenting or personal effort.

While the cause of this brain dysfunction remains unclear, genome-wide association studies (GWAS) have identified many genes associated with developmental disorders. It is thought that mutations in these genes may disrupt their proper functioning and affect brain functions.

Therefore, it may be possible to estimate the risk of developmental disorders by testing for mutations in genes associated with developmental disorders.

There is a condition called phenylketonuria, which causes abnormalities in amino acid metabolism. This condition occurs when there is a mutation in the gene that encodes for the enzyme responsible for metabolizing the amino acid phenylalanine. If the enzyme does not have sufficient activity to metabolize phenylalanine, abnormal accumulation of phenylalanine occurs, leading to developmental disorders.

However, near-normal development can be expected with appropriate treatment, such as the provision of special phenylalanine-free milk. Because treatment is more effective if started early, mass screening tests for newborn babies are carried out within a few days after birth. If the condition is known before birth, the special milk can be given soon after birth, which may lead to better treatment outcomes.

Therefore, if it is possible to know the risk of developmental problems before birth, parents can provide a suitable environment for the child earlier, which may minimize the effects.

Until now, testing for genetic mutations required a large amount of DNA, took a long time, and was very expensive. Therefore, testing for mutations in multiple genes before birth is almost impossible.

However, PCR has made it possible to quickly amplify tiny amounts of DNA enough for sequencing. In addition, the widespread use of next-generation sequencing (NGS) has made it possible to sequence many genes quickly and cheaply. The rate at which the cost of reading a sequence falls outstripping the computing power increase predicted by Moore's Law. As a result, it is possible to sequence the entire genome individually.

Thus, detecting mutations in genes associated with developmental disorders from foetal cells in amniotic fluid has become possible.

There are two types of amniotic fluid tests for developmental disorders: WGS (whole genome sequencing) and panel testing.

WGS reads the whole genome sequence, not just the exons that encode proteins but also the introns, and detects mutations associated with developmental disorders. The panel test reads only the sequences of exons and their small adjustment regions and detects mutations associated with developmental disorders.

Therefore, WGS tends to be more expensive than a panel test. In addition, mutations unrelated to developmental disorders may be found, and there is a possibility of feeling psychological stress from knowing about the possible onset of another disease. However, even if one carries a mutation, one can live a normal life without developing the disease, as the penetrance of mutations varies from disease to disease.

The panel test offers cost savings compared to WGS. Also, because it focuses on genes associated with developmental disorders, it generally gives more accurate results by reading deeper or obtaining more data than WGS. The chance of finding mutations not associated with developmental disorders may be lower with WGS.

There is a risk of miscarriage when amniotic fluid is collected. However, the method used to collect the amniotic fluid is the same as for a usual amniocentesis, so the risk of miscarriage is not thought to be higher than for that amniocentesis.

In addition, mutations in genes unrelated to developmental disorders may be found, leading to psychological stress. Most mutations are inherited from both parents, and there is a possibility of psychological distress from knowing that one or both parents carry mutations found in this test.

The cause of developmental delay is not fully understood. Therefore, if no mutations are found in this test, the possibility of a developmental disorder cannot be ruled out. Conversely, even if mutations are found in this test, it is difficult to predict the severity of the disorder. Therefore, even if mutations are found, there is still a possibility that the child will have a developmental level similar to that of a negative child, indicating a very mild degree of the disorder.

Sequencing accuracy is not 100%. Therefore, the possibility of not detecting existing mutations cannot be ruled out. Conversely, we cannot rule out the possibility that a normal sequence may be judged as a mutation.