Genetic testing
The main diagnostic method for determining whether someone has a CHD2-related disorder is by genetic testing. This involves providing a blood or saliva sample which is analysed in a genetics laboratory either using targeted gene testing, epilepsy gene panel testing, whole exome sequencing or whole genome sequencing.
These tests are able to confirm or rule out the presence of a CHD2-related disorder or indicate a Variant of Uncertain Significance (VUS). A VUS is a variant that has been identified during genetic screening but it is unclear whether that variant is actually the cause of a particular health condition. VUS are often re-interpreted at a later date when more information becomes available.
On the whole, CHD2 related disorders are predominantly the result of random, spontaneous de novo mutations on the CHD2 gene which lead to a change in the genetic code. ‘De novo’ means new, in other words the mutation has not been inherited from either parent. In order to determine this, both biological parents would need to be genetically tested.
For the last ten years it has generally been an accepted genetic principle that if a biological parent also has the same CHD2 variant but without any of the diagnostic characteristics of their offspring, then it was unlikely that this CHD2 mutation was the cause of their disorder. More recently, genetic research has revealed that a CHD2-related disorder can be inherited from an unaffected parent in a very small number of cases.
A DNA Methylation Episignature test may be useful in cases where there is a Variant of Uncertain Significance (VUS) or where a parent has the same CHD2 variant as their offspring but without the same clinical symptoms. The methylation test can establish whether the CHD2 variant is the cause of the symptoms or not, since CHD2- related disorders have a very strong methylation episignature.
It is hoped that this will soon be available on the NHS (watch this space).
To learn more about genetic testing:
- www.curechd2.org/chd2-how-to-test
- www.nhs.uk/conditions/genetic-and-genomic-testing/
- geneticalliance.org.uk/support-and-information/genetic-services-and-testing/nhs-genetic-services-in-the-uk/
Definitions
- Targeted gene testing – used when a specific genetic mutation is suspected based on symptoms.
- Epilepsy gene panel – test involves analysing the most common genes associated with epilepsy.
- Whole exome sequencing – a technique used to sequence just selected regions of DNA, the protein coding regions also known as the exome.
- Whole genome sequencing – examines the entire DNA sequence including coding and non-coding regions. It can be used to identify rarer mutations not identified by whole exome sequencing.
- Variants of uncertain significance – a variant has been identified but it is unclear whether that variant is actually the cause of that health condition.
- DNA Methylation episignatures – are detectable in peripheral blood. CHD2 has a very strong distinct episignature which can help determine whether your offspring’s mutation is disease-causing or not.