Person Who Lived 800 Years Ago Caused Modern-day Seizure Disorder, Scientists Say

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Australian scientists believe they have 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 about 800 years ago. The discovery is particularly noteworthy because inherited conditions of this type usually do not survive as long long in the population.

Epilepsy is an umbrella term for recurrent bursts of abnormal brain activity that trigger neurological symptoms, primarily seizures. It can have many different causes, including variations in our genes passed down between families. When these seizures are accompanied by fever, they are also called febrile seizures.

This new study, led by researchers at the University of Melbourne Center for Epilepsy Research, examined cases of childhood febrile seizures strongly linked to the SCN1Bc.363C>G variant. This variant has been found among several unrelated families in Australia, the United Kingdom, and the United States. families had a long history of early onset epilepsy, and the disorder appears to be a dominant genetic condition, meaning a disease that can be caused by a single copy of the wrong gene. But the researchers were curious whether this mutation had been passed down through a single common ancestor to these affected families or whether it had arisen independently multiple times in human history.

The group attempted to trace the lineage of the SCN1Bc.363C>G variant in 14 families with these seizures. They also analyzed genomic data from the UK Biobank, a large-scale, long-term study of people’s health that also collects their genetic information.

Within the biobank, the researchers identified 74 other individuals carrying the same variant. And all of these people had similar patterns of other genetic variations surrounding the variant, a grouping of genes known as a haplotype. It is very unlikely that all of these people have the same common haplotype without having a common ancestry, say the researchers, meaning that the existence of this genetic condition today is likely due to a single ancestor, also known as founding event name. And as far 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 properly attributed to a single founding event. But these disorders tend to appear later in life (after a person has already reproduced) or be recessive, meaning they only cause disease when someone inherits both copies of the wrong variant. It is therefore very unusual to see the same thing with a damaging dominant mutation that appears in childhood. Often, these mutations are eliminated in a short time, since those affected would be less likely to survive to adulthood and pass the mutation on to the next generation, an example of natural selection.

This mutation, the authors speculate, may have persisted because most people with it experience relatively mild seizures. OOnly about 70% of people with the mutation seem to get sick, which is called incomplete penetrance. In other words, this mutation could cause problems, but not enough to prevent people who have it from living their lives and passing on their genes.

In addition to learning more about this disease, the authors say their findings could have wider implications. There may very well be other genetic mutations that similarly persist in the population at low levels, but which could in fact prove to be more harmful than currently assumed.

“These results suggest that 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.

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