What Can Whole Exome Sequencing Diagnose?

Whole Exome Sequencing: A Breakthrough in Diagnosing Genetic Disorders

Whole Exome Sequencing (WES) is changing how doctors diagnose genetic conditions. It examines the exome closely, which is a part of DNA that codes for proteins. WES constitutes only 1-2% of the total genome, but that is where 85% of known disease-causing mutations are found.

What is Whole Exome Sequencing?

Whole Exome Sequencing (WES) is a genetic test. It sequences the exons, which are the protein-coding parts of genes, and analyses them for disease-causing genetic variants. The exons guide the body on how to make proteins. If something goes wrong in an exon, it can lead to disease. ssists in predicting how a disease may prog

Doctors use WES when they suspect a genetic disorder, especially when the symptoms are hard to explain. This method is helpful when previous tests have not given answers.

What Diseases Can WES Help Detect?

WES is beneficial when symptoms do not point to one condition. It helps doctors find a genetic cure for many rare, inherited or complex diseases that are otherwise difficult to diagnose.

Here are a few key categories of diseases that WES can help identify:

• Neurological Disorders – WES helps diagnose epilepsy, autism, ataxia or intellectual disability.
• Metabolic Conditions – A few examples of such conditions are mitochondrial diseases or enzyme deficiencies.
• Skeletal and Muscular Disorders – WES helps diagnose conditions like muscular dystrophy and osteogenesis imperfecta, which affect the bones and muscles.
• Cardiac Conditions – It can uncover inherited heart problems, including certain arrhythmias and cardiomyopathies.
• Vision and Hearing Loss – WES can help find genetic mutations which cause congenital or progressive vision and hearing problems.
• Immunodeficiencies – It helps to identify faults in genes which weaken the immune system and that lead to repeated or severe infections.
• Rare Cancers – WES may also help determine inherited gene mutations that increase an individual's risk of developing certain types of cancer.

What are the benefits of whole exome sequencing?

The Whole Exome Sequencing offers a lot of advantages that can improve diagnosis, treatment and family planning for individuals with genetic conditions. Here are a few benefits of them:

• WES focuses on the coding regions of DNA, where most of the disease-causing mutations are prevalent.
• It helps to diagnose rare or complex genetic conditions more quickly than traditional tests.
• It can reduce the need for multiple visits to clinics.
• Supports a personalised treatment by identifying specific genetic causes.
• By providing a precise diagnosis, WES can sometimes help predict disease progression and inform treatment strategies, especially if the condition is known to respond to specific therapies.
• It offers valuable information for family planning and assessing inherited risks.

What are the limitations of whole exome sequencing?

While powerful, whole exome sequencing has a certain number of limitations that affect the ability to detect all types of genetic changes or conditions. Here is a list of limitations of WES:

• Only analyses exons and missing mutations in the non-coding or regulatory regions.
• May not detect large structural changes, repeat expansions or rare variant types.
• Can return inconclusive results, such as variants of uncertain significance (VUS).
• Interpretation of results requires genetic counselling and an expert analysis.
• Unexpected findings unrelated to the original reason for testing can arise.
• Ethical and emotional challenges can occur, particularly with secondary findings.

Who Should Consider Whole Exome Sequencing?

WES can be a powerful diagnostic tool. However, it is most helpful for specific groups of people. Here is a list of some of the main situations where WES may be considered:

• Children with Developmental or Neurological Issues : WES is often recommended for children who have developmental delays, intellectual disabilities, autism spectrum disorders or unexplained seizures. These symptoms may point to underlying genetic conditions which other standard tests cannot detect.
• Adults with Undiagnosed or Inherited Conditions : Adults who have a long-standing, unexplained medical issue may benefit from WES. It is more so if the symptoms suggest a genetic disorder. It is also useful when there is a family history of a rare disease.
• Families with a History of Genetic Disorders : If a genetic condition runs in the family, WES can help clarify the risks for current and future children. It can also help to identify carriers.
• Newborns and Prenatal Cases : WES is helpful in urgent situations, like having newborns with unexplained illnesses or when prenatal scans detect abnormalities.
• People Seeking Answers or Guidance : Anyone who has a suspected genetic condition and wants clear information about diagnosis, treatment options or reproductive planning should consider speaking to a genetic specialist about WES.
• Previous Inconclusive Tests : WES is helpful if the earlier genetic tests returned negative or unclear results. It offers a broader and deeper look.

The whole exome sequencing is a powerful tool. It helps to uncover the genetic basis of many rare and complex conditions. WES is often the key to getting a long-awaited diagnosis. However, WES is just a part of the puzzle. It works best alongside clinical assessments, family history and an expert interpretation.