January 2023

Whole exome sequencing (WES) is a powerful genetic testing technique that is increasingly being used in clinical practice. This method allows for the identification of genetic mutations in the exome, which is the portion of the genome that codes for proteins. WES can be used to diagnose rare genetic disorders and inherited cancers, identify inherited genetic risks, and guide personalized treatment decisions. One of the main advantages of WES is its ability to identify genetic mutations that may not be detected by other testing methods. This is particularly useful for patients with rare genetic disorders, as WES can be used to identify mutations in genes that are not typically tested for in standard genetic testing. In addition, WES can also be used to identify inherited genetic risks, such as mutations in genes that are associated with an increased risk of certain diseases. WES is also being used to guide personalized treatment decisions. For example, WES can be used to identify genetic mutations that are associated with resistance to certain drugs. This information can be used to guide treatment decisions and improve patient outcomes. Additionally, WES can be used to identify genetic mutations that may predict a patient’s response to a specific treatment. In addition, WES can help identify novel genetic variations that drive the growth and progression of cancer. By identifying these genetic variations, researchers can develop new targeted therapies to treat cancer and improve patient outcomes. WES is an important tool in clinical practice that can help physicians and genetic counsellors make more informed decisions about the care of their patients. By identifying genetic variations that are associated with a wide range of inherited disorders, WES can help improve the diagnosis and treatment of genetic conditions, leading to better outcomes for patients. References

The American College of Medical Genetics and Genomics (ACMG) has recently released new guidelines that strongly recommend the use of noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities. This is a significant shift in the field of prenatal testing, as it marks a shift away from traditional invasive testing methods such as amniocentesis and chorionic villus sampling (CVS) towards safer, non-invasive options. NIPS is a screening test that uses a blood sample from a pregnant woman to analyze the cell-free DNA (cfDNA) of the fetus. The test can detect chromosomal abnormalities such as fetal trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) as well as fetal sex chromosome abnormalities (aneuploidy) with high accuracy. The test can be performed as early as 10 weeks of pregnancy and does not carry the risk of miscarriage associated with invasive testing methods. The ACMG’s new guideline recommends that all pregnant women, regardless of their age or risk factors, should be offered NIPS as a first-line option for prenatal testing. This is a significant shift from the previous guideline, which only recommended NIPS for women at increased risk of chromosomal abnormalities. The new guideline also recommends that women who receive a positive NIPS result should be offered diagnostic testing to confirm the result. The move towards non-invasive prenatal testing is a significant step towards improving the safety and accessibility of prenatal testing. NIPS is not only safer for the pregnancy, but it also eliminates the need for invasive procedures which can cause emotional and physical distress to the expecting mother. Additionally, NIPS allows for earlier detection of chromosomal abnormalities, allowing parents to make informed decisions about their pregnancy and to plan for the care of their child. One of the concerns with NIPS is that it can produce false-positive results, which can cause anxiety and uncertainty for the expecting parents. However, with the recent advancements in technology, the false-positive rate has decreased significantly and it is expected to continue to improve. The ACMG working group cites evidence that, for singleton pregnancies, the detection rate of NIPS for Trisomy 21 is 98.8%, for Trisomy 18 is 98.83%, for Trisomy 13 is 92.85% and for sex chromosome abnormalities is 99.6%. Moreover, it is essential to note that NIPS is not a diagnostic test, but rather a screening test, it is meant to identify high-risk pregnancies, and further diagnostic testing is required for confirmation. The ACMG’s new guideline on NIPS is a significant development in the field of prenatal testing. The organization’s recommendation carries a lot of weight and is likely to be adopted by healthcare providers and insurance companies. This will make NIPS more widely available and accessible to expecting parents, and it will improve the safety and accuracy of prenatal testing. GeneSpectrum’s NGS data analysis platform provides accurate and up-to-date variant annotations supported by ACMG guidelines. To know more, reach out to us at contact@genespectrum.in