Mitochondrial DNA disease is caused by a mutation in your mitochondrial DNA.
Most cases of mitochondrial DNA disease will have been maternally inherited which means the mutation has been passed down from the mother to child. This is because we inherit our mitochondrial DNA from our mothers only.
In this situation, all children may have the mutation but some of the children may be severely physically affected and others not affected, due to the varying level of mutation passed down from the mother to different children.
Mitochondrial Diseases that can be inherited in this way include Leighs syndrome, MELAS, MIDD, MERRF, NARP & LHON.
It is also possible (although less likely) that mitochondrial DNA disease might have happened sporadically. In this situation, the affected person will be the only person in their family to have the disease and the mutation will have happened spontaneously during conception and not have been passed down from the mother.
Mitochondrial Diseases that can be inherited in this way include Pearson's syndrome & Kearns-Sayre Syndrome.Back to top
Mitochondrial Disease may also be caused by a mutation in the nuclear DNA.
It is usually assumed that nuclear DNA mutations are responsible for disease once testing has ruled out faults in the mitochondrial DNA. Despite this, many families may still not know the name of the gene that caused the disease because even with sophisticated gene sequencing techniques, identification can be challenging.
Nuclear DNA mutations may be inherited from parents in a number of different ways: Recessive, Dominant or X-linked.
Autosomal Recessive Inheritance
With autosomal recessive inheritance, both parents carry a single faulty copy of the gene and also a healthy gene.
The normal gene in a carrier usually supplies enough normal protein to avoid the signs and symptoms of the disease.
With each pregnancy a carrier of a faulty gene has a 50% (one in two) chance of passing the faulty gene to the child. If the child inherits the faulty gene, he or she will also be a carrier.
When both parents are carriers, there is a 25% (1 in 4) chance in every pregnancy that the child will inherit two faulty genes and will, therefore, have the disease.
There is also a 25% chance that the child will inherit two normal genes and will not have the disease nor be a carrier.
There is a 50% chance that the child will inherit one faulty gene and will be a carrier which may have implications for future generations.
Mitochondrial Diseases that can be inherited in this way include Leigh syndrome, Alper's disease, MIRAS, SANDO, CPEO.
Autosomal Dominant Inhertiance
With dominant inheritance, only one copy of the faulty gene is required in order to develop Mitochondrial Disease. This means that each person with the disease has a 50/50 chance of passing on the gene to any children they may have.
Additionally, any child that inherits the faulty gene may develop the disease, and, in turn, have a 50/50 chance of passing on the faulty gene.
However, with one normal and one faulty gene, all of these individuals may or may not develop symptoms of disease.
If they do develop disease, the severity can vary markedly. In regards to the highly variable manifestations among individuals with a faulty gene, autosomal dominant and maternally inherited mitochondrial disorders are similar. However, in autosomal dominant, but never in maternally inherited conditions, boys can pass the faulty gene and disease to their children.
Mitochondrial Diseases that can be inherited in this way include late onset CPEO.
In X-linked disease, the genetic defect is located on the "X" chromosome and usually affects males only.
This happens because females have 2 X chromosomes - 1 from the mother and 1 from the father, whereas males only have one X chromosome, inherited from their mother (they get a "Y" chromosome from their father).
Females with one normal X chromosome and one faulty X chromosome generally do not manifest the disorder because of the presence of the normal gene. However, these females are at risk of passing on genetic disease and are called "carriers".
On the other hand, since a male only has one X chromosome, if it is faulty he has no normal copy and will develop the disease represented by the genetic fault (mutation).
If a female carrier has children, there is a 50/50 chance that she will pass on the faulty gene to her children. If that child happens to be a girl and inherits the gene, she too will become a carrier.
If the child is a boy and inherits the faulty gene, he will develop the disease.
Pyruvate Dehydrogenase Deficiency (E1alpha) is inherited this way.Back to top