Whole Exome • Next Lab

A diagnostic test that enables sequencing of the coding regions of approximately 22,000 genes in the human genome. This coding portion accounts for 2% of the genome. Of these nearly 22,000 genes, around 5,000 are currently known to be associated with disease, while the remainder have no confirmed pathological association to date. However, the number of disease-associated genes is constantly increasing, as new gene-disease links continue to be discovered.

When is Whole Exome testing recommended?

Complex phenotypes with multiple differential diagnoses
Genetically heterogeneous disorders
Previous inconclusive genetic testing
Suspected genetic disorder for which no specific test is available
Suitable for both single-patient and trio-based analysis

Which genes are analysed?

The analysis involves sequencing the 22,000 coding genes. All variants are investigated based on their potential relevance to the clinical phenotype under investigation. At least 95% of all coding exons in the human genome will be covered.

What are the possible outcomes of Whole Exome sequencing?

This test generates a large volume of data, which may present challenges in terms of interpretation and management. It is generally recommended to confirm any mutation detected through NGS using Sanger sequencing. In addition, it is generally necessary to establish the segregation of the mutation(s) within the family in order to determine which of the identified mutations is actually responsible for the condition. This is why Whole Exome sequencing is often performed on a family trio (proband and both biological parents).

The analysis may lead to three possible outcomes:

1

One or more genetic alterations are identified, which are interpreted as possible causes of the condition affecting the proband. This may assist in refining the clinical diagnosis and help assess the risk of recurrence in future pregnancies.

2

One or more genetic alterations are identified, but their role in relation to the condition is not clearly interpretable. In such cases, further investigations may be necessary to clarify the significance of these alterations. The patient will be informed of the findings and updated over time as interpretation evolves.

3

No relevant genetic alterations are identified to explain the condition under investigation. However, the results may be re-evaluated in the future as new information becomes available about the condition and the genes involved. The patient will be informed if relevant new findings emerge.

In addition to these three possible outcomes, there is a possibility of incidental findings — that is, the discovery of genetic alterations unrelated to the condition under investigation but potentially relevant to your health or that of your family members. Examples include genetic alterations associated with a predisposition to late-onset cancers or neurological disorders, or being a healthy carrier of a genetic condition which may not affect your health, but could have implications for reproductive risk (the transmission of diseases to your offspring).

The test is performed at the Pavia operational site, which implements a quality management system in accordance with ISO 9001:2015 and SIGUCert standards