Genetic disorders

What is DNA?

Our DNA is like a great library that contains all the information that makes our body work. Each of the books on the shelves are our genes, and an error in one of them is called mutation. These mutations cause genes to not be read correctly, and alter the manufacture of proteins and, therefore, also some functions of our body, leading to different diseases.

Our body is protected from these genetic disorders by having duplicate DNA, that is, we all have two copies of each gene, one inherited from our father and the other from our mother. This means that the appearance of genetic disorders is conditioned by the number of copies we have altered.

• Dominant expressions: This pattern occurs when a mutation in a single copy is sufficient to express the disease. For example, when the father is affected by the disease and the mother is not. In this case half of their children will be affected and the other half will not.
• Recessive expression: In this case, it is necessary for both copies of a gene to be altered for the disease to occur, that is, the mother and the father's copy must have the mutation. This means the father and mother will be carriers of the disease, and as a result, 25% of their children will be affected by the disease, 50% will be carriers and the other 25% will not be affected at all.
• Expression linked to the X chromosome: This chromosome determines the sex of living beings. Female people have two X chromosomes and those of male sex have an X and Y, becoming more vulnerable to mutations because they have only one copy. Diseases caused by mutations in the X chromosome can follow a dominant or recessive pattern:
  • In the dominant pattern, for example, if the father is affected and the mother is not, the women will be affected and the men will not. And should the mother be affected and the father is not, half of the children will be affected and the other half will not.
  • In the recessive pattern, if the father is affected by the disease and the mother is not, the women will be carriers and the men will not be affected. And should the mother be a carrier and the father be unaffected, half of the children will not be affected, half of the males will be affected and half of the women will be carriers.
• Mitochondrial expression: This happens when there are alterations in a small proportion of the DNA found in the mitochondria of the cell, that is, mitochondrial DNA. It is a particular pattern, since mitochondria are inherited solely from the mother and, therefore, only women can transmit the mutation. For example, if the father has affected mitochondrial DNA and the mother does not, no child will be affected. And if the mother is affected, but the father is not, all children will be more or less affected depending on the number of damaged mitochondria.
• De novo mutations: Sometimes mutations occur spontaneously in the affected child and are absent in the DNA of both parents. However, this mutation can be transmitted if the affected child has future offspring. In fact, all mutations inherited from parents were, at some point, de novo, and spontaneously appeared in a family ancestor.

Are there other factors that manifest a genetic disorder?

In addition to the main hereditary types, there are cases that do not follow these basic rules. This is due to the existence of other less known factors that make each person manifest the disease in different ways:

• Penetrance: This is defined as the proportion of individuals with a mutation presenting the disease. Therefore, there are genes that present 'incomplete penetrance', that is, not all individuals manifest the symptoms of the disease.
• Mosaicism: This phenomenon occurs due to a mutation that appears very early in the development of the foetus and causes not all cells in the body to contain the mutation. Thus, expression of the disease will vary depending on the type of cells affected.
• Genetic impression or imprinting: This is a genetic phenomenon through which the expression of certain genes is conditioned by the sex of the parent from which it was inherited. For example, in the case of myoclonic dystonia, the copy of the inherited gene from the mother is silenced. In this way, a person who has a mutation in the maternal copy of the gene will not show symptoms of the disease, although they will be a carrier and can transmit it to their offspring.

How is a genetic disorder diagnosed?

In recent years, the study of genetic mutations has evolved exponentially, thanks to the appearance of improved techniques that allow us to sequence our genome, all our DNA. Sequencing is basically 'reading' and knowing the exact sequence each of our genes has. Therefore, depending on the situation, we will analyse a specific gene or we will have to go further and read larger areas of the genome. That is why we have several strategies:

• Array-CGH analysis: This technique allows us to review some library shelves and check if a book is missing. Sometimes, neurological diseases may be due to the fact that several whole genes are missing, that is, several books in the library.
• Complete exome analysis: When we carry out this analysis, we read all the books in the library to look for spelling mistakes in one of the 8,000 genes we know can cause a genetic disorder.
• Complete genome analysis: There are times when we cannot find any errors in the books and we must review the other elements in the library such as bookshelves, furniture, etc. In our genome, in addition to genes, there are regions that act as spacers, regulators, and many other sequences with yet unknown functions, that could have an important impact on our body and that we must take into account.

The appearance and implementation of all these clinical techniques has led to giant leaps in the genetic diagnosis of many diseases, including dystonia and other movement disorders.

What is the treatment for a genetic disorder?

When we talk about genetic diseases we must be aware that the alteration is present in all the cells of our body and cannot be eliminated. New gene therapies focused on correcting the genetic error in some neurological diseases have been in development over the last few years.