DNA (deoxyribonucleic acid) is the carrier of our genetic information. DNA is arranged into 23 pairs of chromosomes, with one of each pair inherited from each parent. Everyone has their own unique set of DNA – unless you have an identical twin!
DNA is used as a template for making proteins. It’s like the instruction manual to your entire body and every process that occurs inside it.
Before DNA can make proteins, it is first transcribed into ribonucleic acid (RNA). The strand of RNA is translated to make proteins. It does this using codons, which are made into a specific amino acid (or building block of protein). These different amino acids have different jobs.
There are a group of these amino acids whose specific job is to say STOP!! This signifies the end of the protein, or that it is time for the body to stop making it.
There are many different mutations of AHDC1 present in individuals with XGS.
At this time it is not known how each of the mutations will affect them. But what they mostly have in common is that there was some change to the sequence of DNA in the AHDC1 gene that has led to a premature stop codon being made, and so the resulting protein is too short.
When proteins are too short, they don’t look the same to the body and can’t be used in the usual way. They can sometimes even cause damage, because they can interfere with other processes of the body. The interesting thing about individuals with XGS is that they all still have one complete copy of AHDC1. That is, the AHDC1 gene is only damaged on one copy of Chromosome 1 and complete on the other copy. For this reason, the syndrome is considered ‘heterozygous’ and ‘dominant’ – in other words, only one faulty or incomplete copy of the AHDC1 gene is needed to cause an individual to have Xia-Gibbs Syndrome.
There are also some people with XGS who, rather than having a shortened or truncated copy of the AHDC1 gene, are missing one copy of the gene completely, due to what is called a ‘deletion’. So far, researchers have not yet determined whether this results in the same symptoms.
Mutations are very common in our DNA and that is part of what makes all of us unique, but mutations that cause changes in proteins are a common cause of genetic diseases.
At this point, it is suspected that the vast majority of cases of XGS are due to a ‘de novo’ or new mutation. This means that it was a spontaneous mutation that occurred in either the sperm or the egg cell or in the fertilized egg, and was not passed down from either parent. In this case, neither parent would have the mutation, and therefore could not pass it on to any other children they might have.
It is thought that in rare instances, one of the parents of a person with XGS may be ‘mosaic’ for the syndrome. In mosaicism, a portion of the individual’s cells could have the AHDC1 mutation while others do not. If this affects a parent’s reproductive cells, it could increase the chances of the disorder being present in other siblings of the individual with XGS.