Diagnosis and genetic testing

If a disease like Duchenne muscular dystrophy is suspected, it is very important that a diagnosis be made early to ensure the child receives the very best care and management. Understanding a patient’s specific genetic mutation is needed to determine their eligibility to participate in clinical trials and for any new therapies that become available.

Here are the steps a family will typically encounter during diagnosis:

Clinical exam

The first step in diagnosis is a clinical exam, checking the child’s muscles and development.

If the child is showing early signs of Duchenne, the doctor will also ask if anyone in the family has Duchenne, or if any women in the family are known to be carriers. If there is a family history of Duchenne, the child should have more testing, even if he is younger than five.

Check creatine kinase levels

If your doctor suspects Duchenne, he or she will draw blood to test the enzyme called creatine phosphate kinase (also known as CPK or CK) that is released from the muscle when it is damaged. Boys with Duchenne often have CK levels 10 to 100 times the normal range. A very high CK level will tell the doctor that the child has a muscular disease (myopathy). To find out if the disease is Duchenne, the doctor will do another test – either a genetic test or muscle biopsy.

Muscle biopsy

Your doctor may recommend a muscle biopsy, taking a small sample of muscle for analysis. Tests on the muscle biopsy can provide information on the amount of dystrophin present in the muscle cells.

If your child has already received a positive Duchenne diagnosis through genetic testing, a muscle biopsy may not be required. At some centres, the diagnosis of Duchenne may be made by muscle biopsy analysis. Genetic testing after a positive biopsy diagnosis of Duchenne is still essential to determine the specific change in the DNA or genetic mutation causing Duchenne.

Genetic testing

If the child has a very high CK level, genetic testing should be done to look for genetic changes (called mutations) that cause Duchenne.

Genetic testing refers to the analysis of the person’s DNA. It is used to confirm a diagnosis and identifies the specific disease and cause of the mutation. For Duchenne, the dystrophin gene is checked to see if any mutations that keep the gene from working properly can be found. Genetic testing can be done on blood, saliva, muscle, or other tissue.

Different types of genetic tests look for different types of gene changes. Some people with Duchenne need to have more than one test to find the mutation. Genetic testing can determine if your child has one of the two known gene mutations for Duchenne: an exon or nonsense mutation.

Why is genetic testing important?

In Duchenne muscular dystrophy, genetic testing can reveal important information about the disease that will:

  • Provide confirmation of diagnosis and/or carrier status
  • Facilitate participation in clinical trials
  • Confirm eligibility for emerging treatment

Several new therapeutic drugs in development to treat Duchenne require knowledge of the person’s precise genetic mutation, so genetic testing has become important – not only for diagnosis, but for future treatments. Once a diagnosis has been confirmed and genetic testing is complete, the best way to ensure that your child has access to upcoming clinical trials or new treatments that become available is to enroll them in a patient registry.

Learn more about clinical trials and patient registries.

Genetic testing can involve several steps and it is important to have a knowledgeable healthcare provider who can answer questions throughout the process. To learn more about genetic testing and counselling, visit:

Muscular Dystrophy Canada
Canadian Association for Genetic Counsellors
Decode Duchenne

If you or your child has Duchenne muscular dystrophy, you may be eligible to receive genetic testing through Decode Duchenne. This program, offered by Parent Project Muscular Dystrophy in the U.S. and supported by PTC Therapeutics, BioMarin Pharmaceutical and Sarepta Therapeutics, provides genetic testing at no cost to eligible patients in the U.S. and Canada who are unable to access testing due to barriers such as a lack of insurance or insufficient insurance coverage.

EXON AND NONSENSE MUTATIONS

Proteins are essential parts of the body’s cells and play a role in every process occurring within the cell, including the structural or mechanical functions which help maintain the cells’ shape. Duchenne muscular dystrophy is caused by a mutation in the dystrophin gene, located on the human X-chromosome, which codes for the protein dystrophin.

WHAT ARE EXONS?

Genes are divided into sections called exons and introns. Exons are the sections of DNA that code for the protein and are interspersed with introns which are sometimes called “junk DNA.” The introns are cut out and discarded in the process of protein production, to leave just the exons. The dystrophin gene is the largest gene comprised of 79 exons which are joined together like the pieces of a puzzle.

In Duchenne muscular dystrophy, an exon or exons are deleted which interfere with the rest of the gene and prevent the rest of the exon from being assembled. For the dystrophin protein to work, both ends of the gene must have protein. This mutation results in a completely non-functional dystrophin protein and the development of Duchenne muscular dystrophy.

WHAT IS EXON SKIPPING?

Exon skipping is to encourage the cellular machinery to skip over an exon. Molecular patches are used to mask the exon that is needed to skip so that it is ignored during protein production. It is thought that skipping one or two exons would be able to treat around 83 per cent of the genetic errors causing Duchenne muscular dystrophy.

WHAT IS A NONSENSE MUTATION?

A nonsense mutation is a change in the DNA which causes a premature stop signal to occur in a gene and affects the production of protein. A nonsense mutation is when one letter of the DNA blueprint is changed to another letter – like a spelling mistake – to make a signal which stops our cells reading the rest of the blueprint. Research has shown that certain chemicals can encourage cells to ignore this stop signal and carry on reading to the end of the DNA blueprint.