WHAT CAUSES DUCHENNE?

Duchenne is caused by a change to a gene that provides the instructions for the production of the protein called ‘dystrophin’.


As a result very little or no dystrophin protein is produced. Dystrophin normally protects muscle cells from damage and without it, the muscle cells deteriorate and the symptoms of Duchenne muscular dystrophy develop. The genetic change is often referred to as a ‘mutation’


The genetic mutation that causes Duchenne is either:
passed down through the family (inherited), or
caused by a new genetic change that occurs in the child.


The new genetic change is known as a ‘spontaneous mutation’ and this happens in more than one third of Duchenne cases. The dystrophin gene is particularly susceptible to new mutations because of its large size. This explains why Duchenne can appear in a family with no prior history of the condition in previous generations. The spontaneous genetic change happens very early in development – in the egg that is fertilised at the beginning of a pregnancy. New mutations may also occur in the mother, causing her to be the first carrier in the family.

NOTE: the likelihood of the possible four outcomes in the diagram is equal, so in each pregnancy there is a one in four chance of having a boy with Duchenne.

WHAT CAUSES DUCHENNE?

Duchenne is caused by a change to a gene that provides the instructions for the production of the protein called ‘dystrophin’.


As a result very little or no dystrophin protein is produced. Dystrophin normally protects muscle cells from damage and without it, the muscle cells deteriorate and the symptoms of Duchenne muscular dystrophy develop. The genetic change is often referred to as a ‘mutation’


The genetic mutation that causes Duchenne is either:
passed down through the family (inherited), or
caused by a new genetic change that occurs in the child.


The new genetic change is known as a ‘spontaneous mutation’ and this happens in more than one third of Duchenne cases. The dystrophin gene is particularly susceptible to new mutations because of its large size. This explains why Duchenne can appear in a family with no prior history of the condition in previous generations. The spontaneous genetic change happens very early in development – in the egg that is fertilised at the beginning of a pregnancy. New mutations may also occur in the mother, causing her to be the first carrier in the family.

NOTE: the likelihood of the possible four outcomes in the diagram is equal, so in each pregnancy there is a one in four chance of having a boy with Duchenne.

HOW IS DUCHENNE INHERITED?

In around two thirds of cases of Duchenne the faulty dystrophin gene is passed down through the family. The gene that is affected in Duchenne – the dystrophin gene – is located on the X chromosome. This is one of the chromosomes that determines our gender.

Males have one X chromosome inherited from their mother and one Y chromosome inherited from their father. If their X chromosome contains a faulty dystrophin gene, they will have Duchenne muscular dystrophy.
Females on the other hand, have two X chromosomes, one inherited from each parent. If one X chromosome contains a faulty dystrophin gene the healthy dystrophin gene on the other X chromosome can compensate for it and therefore females usually don’t show any symptoms or symptoms are very mild. These girls are known as carriers and could potentially pass the condition on to their sons.

If a male with Duchenne were to have children with a non-carrier female, their sons would not inherit the condition and their daughters would all be carriers. It is important to remember that Duchenne is nobody’s fault and nobody did anything wrong to cause it. An appointment with a genetic counsellor can help with understanding the inheritance of Duchenne.

WHAT IS GERMLINE MOSAICISM?

Mosaicism in genetics is when a proportion of cells are genetically different to the rest. For example in a black and white cat, some of the hair cells have the genetic code to make black fur and some have the instructions to make white fur. Germline refers to egg and sperm cells.
In Duchenne, germline mosaicism refers to a proportion of a woman’s eggs containing the mutation that causes Duchenne. It is thought that around 15 percent of women who have a son with Duchenne, but her blood tests negative for being a carrier, have germline mosaicism. Germline mosaicism is of concern because even though a woman is not a carrier, there is an increased risk of having another son with Duchenne, or daughters who are carriers. However, it is practically impossible to test for germline mosaicism (unless a couple goes through IVF and has genetic testing done), so it is difficult to give an accurate estimate of the risk.

WHAT ARE THE TYPES OF MUTATIONS THAT CAUSE DUCHENNE?

The dystrophin gene has 79 pieces called ‘exons’. Each exon contains on average a few hundred ‘letters’ of genetic code.

There are three different types of genetic changes (mutations) that cause Duchenne:
Large deletions (missing whole exons)
Large duplications (additional whole exons)
Small point mutations (changed, inserted or deleted letters of code)
Large deletions are the most common type of mutation, accounting for around 80 percent of mutations.
The other types are rarer – point mutations (10 to 15 percent) and large duplications (5 to 11 percent).

HOW DO MUTATIONS AFFECT THE DYSTROPHIN GENE?

The dystrophin gene has 79 pieces called ‘exons’. Each exon contains on average a few hundred ‘letters’ of genetic code.
The letters of genetic code contained within a gene are “read” by the body in “sentences” of three-letter words.

HOW IS DUCHENNE INHERITED?

In around two thirds of cases of Duchenne the faulty dystrophin gene is passed down through the family. The gene that is affected in Duchenne – the dystrophin gene – is located on the X chromosome. This is one of the chromosomes that determines our gender.

Males have one X chromosome inherited from their mother and one Y chromosome inherited from their father. If their X chromosome contains a faulty dystrophin gene, they will have Duchenne muscular dystrophy. Females on the other hand, have two X chromosomes, one inherited from each parent. If one X chromosome contains a faulty dystrophin gene the healthy dystrophin gene on the other X chromosome can compensate for it and therefore females usually don’t show any symptoms or symptoms are very mild. These girls are known as carriers and could potentially pass the condition on to their sons.

If a male with Duchenne were to have children with a non-carrier female, their sons would not inherit the condition and their daughters would all be carriers. It is important to remember that Duchenne is nobody’s fault and nobody did anything wrong to cause it. An appointment with a genetic counsellor can help with understanding the inheritance of Duchenne.

WHAT IS GERMLINE MOSAICISM?

Mosaicism in genetics is when a proportion of cells are genetically different to the rest. For example in a black and white cat, some of the hair cells have the genetic code to make black fur and some have the instructions to make white fur. Germline refers to egg and sperm cells. In Duchenne, germline mosaicism refers to a proportion of a woman’s eggs containing the mutation that causes Duchenne. It is thought that around 15 percent of women who have a son with Duchenne, but her blood tests negative for being a carrier, have germline mosaicism. Germline mosaicism is of concern because even though a woman is not a carrier, there is an increased risk of having another son with Duchenne, or daughters who are carriers. However, it is practically impossible to test for germline mosaicism (unless a couple goes through IVF and has genetic testing done), so it is difficult to give an accurate estimate of the risk.

WHAT ARE THE TYPES OF MUTATIONS THAT CAUSE DUCHENNE?

The dystrophin gene has 79 pieces called ‘exons’. Each exon contains on average a few hundred ‘letters’ of genetic code.

There are three different types of genetic changes (mutations) that cause Duchenne:
Large deletions (missing whole exons)
Large duplications (additional whole exons)
Small point mutations (changed, inserted or deleted letters of code)
Large deletions are the most common type of mutation, accounting for around 80 percent of mutations.
The other types are rarer – point mutations (10 to 15 percent) and large duplications (5 to 11 percent).

HOW DO MUTATIONS AFFECT THE DYSTROPHIN GENE?

The dystrophin gene has 79 pieces called ‘exons’. Each exon contains on average a few hundred ‘letters’ of genetic code.
The letters of genetic code contained within a gene are “read” by the body in “sentences” of three-letter words.