Genetic tests are usually performed on a blood sample.
The tests aim to identify which faulty gene is causing a condition and the precise nature of the genetic fault, in other words, the mutation. There are several different types of mutation, which are named for their effect on the DNA.
For instance, a ‘deletion mutation’ is caused when some of the DNA is deleted and ‘duplications’ occur when part of the DNA is repeated. The clinical diagnosis suggests which gene (or genes) should be tested but often it does not point towards a single gene.
For example, the early symptoms of some cases of limb girdle muscular dystrophy can be hard to distinguish from other conditions like Becker muscular dystrophy.
Some neuromuscular conditions can be caused by mutations in any one of several genes.
For example, over 20 different genes are associated with limb girdle muscular dystrophy. In these cases, the gene that is most likely to cause the condition and symptoms observed is tested first.
If no mutation is found, the next most likely gene will be tested, and so on. In this case a diagnosis can take some time, depending on how many genes need to be tested.
Occasionally, if a genetic test is not available through the diagnostic service, samples are sent to laboratories where the DNA is analysed as part of ongoing research.
Sometimes, a clinical diagnosis points clearly in the direction of a single gene.
A clinical diagnosis of Duchenne muscular dystrophy points to the dystrophin gene and testing then focuses on identifying the mutation in that gene. In these cases, testing initially looks for the most common mutations (for example, deletions in Duchenne muscular dystrophy) and gradually works towards rarer mutations.
Despite recent advances in identifying mutations that can cause neuromuscular conditions, clinicians will sometimes test all the known genes and still fail to identify the mutation causing the condition.
Currently, about 50 percent of people with congenital muscular dystrophy do not receive a genetic diagnosis.
Why is a genetic diagnosis important?
A precise genetic diagnosis allows clinicians to give their patients better information about how the condition will progress during their lifetime.
This can help individuals and families to prepare in advance to manage their condition and to make informed family planning decisions. Some clinical trials require prospective participants to have a genetic diagnosis.
This might be because the therapy being tested targets the underlying genetic cause of the condition. For example, exon skipping therapies for Duchenne muscular dystrophy are mutationspecific. This means that when these therapies are made available, they will potentially benefit only people with certain mutations.