Scientists in Australia believe that they’ve discovered the centuries-old origins of a rare form of childhood epilepsy caused by a genetic mutation: a single common ancestor who lived in Britain roughly 800 years ago. The find is especially notable because hereditary conditions of this kind typically don’t survive for so long in the population.
Epilepsy is a broad term for recurring bursts of abnormal brain activity that trigger neurological symptoms, most prominently seizures. It can have many different causes, including variations in our genes passed down between families. When these seizures are accompanied by fever, they’re also known as febrile seizures.
This new study, led by researchers at the University of Melbourne’s Epilepsy Research Center, looked at cases of childhood febrile seizures strongly tied to the SCN1Bc.363C>G variant. This variant has been found among multiple unrelated families in Australia, the UK, and the U.S. Many of the families had a long history of early epilepsy, and the disorder appears to be a dominant genetic condition, meaning a disease that can be caused by only having one copy of the bad gene. But the researchers were curious whether this mutation had been passed down by a lone common ancestor to these affected families or if it had independently arisen multiple times in human history.
The group tried to trace back the lineage of the SCN1Bc.363C>G variant in 14 families with these seizures. They also analyzed genome data from the UK Biobank, a large-scale and long running study of people’s health that also collects their genetic information.
Within the biobank, the researchers identified another 74 individuals with the same variant. And all of these people had similar patterns of other genetic variations surrounding the variant—a grouping of genes that’s known as a haplotype. It’s very unlikely that all of these people would have the same common haplotype without having some shared ancestry, the researchers say, meaning that the existence of this genetic disease today is probably due to just one ancestor, also known as a founder event. And as near as they can tell, this ancestor lived about 800 years ago.
“Here, we report evidence of a single founder event giving rise to the SCN1Bc.363C>GQ11 variant in 14 independent families with epilepsy,” the authors wrote in their paper, published Tuesday in The American Journal of Human Genetics.
There are other genetic disorders or traits that can be cleanly traced back to a single founder event. But these disorders tend to appear later in life (after a person has already reproduced) or to be recessive, meaning that they only cause disease when someone inherits both copies of the bad variant. So it’s very unusual to see the same with a damaging dominant mutation that shows up in childhood. Often, these mutations are weeded out in a short time, since affected people would be less likely to survive into adulthood and pass on the mutation to the next generation—an example of natural selection.
This mutation, the authors speculate, might have endured because most people with it experience relatively mild seizures. Only about 70% of people with the variant seem to become sick at all, something known as incomplete penetrance. In other words, this mutation might cause trouble, but not enough to have kept people who had it from living their lives and passing on their genes.
Aside from learning more about this disease, the authors say their findings could have broader implications. There may very well be other genetic mutations out there that similarly linger in the population at low levels but which might actually turn out to be more harmful than currently assumed.
“These findings suggest variants present in the population at low frequencies should be considered potentially pathogenic in mild phenotypes with incomplete penetrance and may be more important than previously thought,” they wrote.