Apert syndrome: DNA mutations in testicles blamed – and it gets worse with age

Apert syndrome, a birth defect that stops the skull from growing normally, has been found to be a result of random mutations in sperm. A study has finally discovered why the disease can be found in the children of healthy parents – and it discovered that it is all a game of chance.

The research, published in the journal PNAS, is the first of its kind to show that as sperm accumulate in the testicles, they are subject to random, unprovoked errors in the DNA replication process. These mistakes can ultimately lead to Apert syndrome – a welcomed discovery, as it was previously unknown what caused the genetic disorder.

The University of Oxford researchers compared sperm samples from fathers of healthy children, and from those whose children had Apert syndrome, all ranging in age from 39 to 90 years old. They noted that the sperm sets showed no statistically significant differences, suggesting that the chances of a baby having Apert syndrome had little to do with the health of the parent. However, they did notice that as the mutated DNA begins to increase in number through replication, they can eventually outnumber the 'healthy' DNA. These growths – similar to a tumour growing in size – are called 'selfish growths'.

The researchers also discovered that incorrect copies of the sperm can replicate themselves, due to the gene called FGFR2. This increases the chances of having a baby with the disease.

"The process that gives rise to Apert syndrome happens in every man, meaning any couple could have a child with Apert syndrome, regardless of the health of the parents," said Anne Goriely, a researcher for the study. "I also found that older men tended to produce more of these Apert mutations."

The mutations in the DNA replication process is more likely to occur when the future father is older – similar to how other parts of the body encounters more DNA mutations as we age, including the brain, muscles and liver. This is the first time that scientists have managed to identify the cause of Apert syndrome in children that have been fathered by healthy men.

Selfish growths could be isolated by the scientists. Despite the complexity of tubes inside the testicles, they could identify which sperm were likely to lead to the disorder in children – not just Apert syndrome, but also autism, schizophrenia and even dwarfism.

When asked if this is the first step towards a cure for the disease, Goriely told IBTimes UK: "It is probably a little far-fetched at this point in time. Although we can 'light up' the regions that give rise to mutant sperm, it is not possible to 'eradicate' them, as this material is fixed and cannot be used for downstream applications such as fertilisation.

"The best we can do at this stage is to analyse these selfish growths and the mutation that has caused their occurrence," she added. "This still provides us with useful information as these are the mutations which are most likely to turn up in the fertilised egg."

Apert syndrome is a very rare condition, affecting just one in 65,000 people globally.