DNA (deoxyribonucleic acid)
DNA (deoxyribonucleic acid) is a molecule found in the nucleus of every cell that holds the template for how living organisms are built. It is made up of chemical building blocks and the order, or sequence, of these determines what biological instructions are contained in a strand of DNA.
RNA (ribonucleic acid)
Some types of RNA (ribonucleic acid) are made as temporary templates used to guide the assembly of the building blocks that make proteins. The RNA template follows the instructions contained in the DNA or gene segments.
Genes
Genes are segments of DNA that provide templates (the instructions) for the manufacture of proteins. Mutations or mistakes in a particular gene can mean that the protein that is made will not function properly or will not be made at all, and this can cause disease.
Since the first genes causing NCL were identified in 1995, more than 660 mutations or mistakes in 12 different genes have been discovered. These 12 genes encode or are responsible for the production and function of different proteins.
Chromosomes
Genes are organized and packaged within the cell in structures called “chromosomes.” Humans have 23 pairs of chromosomes. A child will inherit a set of chromosomes; one chromosome comes from their mother, and the other from their father.
Diagnosis
There are certain procedures, which are common to all the forms of NCL. A child or young person will probably have been seen by paediatrician, and/or a paediatric neurologist, because of symptoms such as seizures. Some diagnostic tests are specific for an NCL.
Genetic Diagnosis
- Genetic testing can be used to find out whether a child or young person has a specific genetic mutation or mistake in a particular NCL gene.
- A referral for genetic diagnosis is usually required from a GP, or a Consultant.
- Blood or cell samples will need to be taken and sent to be tested in a genetics laboratory to check for mutations in the specific NCL gene.
This can be a complex process and samples may be sent to specialist centres for analysis. It may take some time, and the results are not always clear and definite.
The Clinical Genetics Department at Great Ormond Street Hospital performs NCL genetic analysis and there is more information on how a sample is analysed on the BDFA website.
Genetic Code
Each gene is composed of a series of building blocks known by letters - adenine (A), thymine (T), guanine (G) and cytosine (C). These correspond to the different bases in the DNA, the sequence of which forms the genetic code. Almost the same letters are found in the template RNA – adenine (A), uracil (U), guanine (G) and cytosine (C).
This string of letters is the genetic code for that particular bit of gene and the tests performed will look for differences in patients who have the disease compared to what it should be in a person without disease.
Diagnostic Reports
Once all of the evidence has been gathered a report detailing the findings is produced, concluding whether the diagnosis has been confirmed or not. This will be sent to the clinician who has made the referral and who will discuss the results with the family. This report will usually contain the following information:
- Referral Reason - this explains why the test is being performed, why it has been requested, and includes any clinical and biochemical information that supports the diagnosis.
- Results – this is a table that details the mutations or mistakes that have been found in the patient using the DNA genetic coding. As the NCLs are autosomal recessive disorders, the genetic test will be looking for the mistakes in each of the two chromosomes, one inherited from each parent.
- Report – this goes into more detail about what has been found and what evidence has been used to reach the conclusion. This can be difficult to interpret and an appointment should always be available for the results to be explained by a qualified professional.
Carrier Screening
The same scientific process used for Genetic Diagnosis, is also used to obtain results for Carrier Testing or Screening. When a diagnosis of NCL is confirmed or suspected other family members may wish to be tested to see if they also carry the same mutation or mistake.
A referral to the local genetic counselling service will need to be made by a GP or Consultant for samples to then be sent for analysis. This service should also provide support and advice in understanding and interpreting the results.