Scientists have recently identified a genetic mutation that causes epilepsy, and is carried by at least 90 people. These mutations are thought to all trace back to a single individual, who probably lived in Britain over 800 years ago and passed it down to offspring, who continued to do that over many generations. The researchers proposed that this mutation has been sustained in a population that is outbred, which is to say, while some of the individuals who now carry the mutation are related to one another, all of the carriers are not part of an inbred or isolated community; nor are they all part of the same big family. The findings have been reported in the American Journal of Human Genetics by an international team of researchers.
The mutation is found in a gene called SCN1B, and carriers of the variant, called p.Cys121Trp, are part of unrelated, multigenerational families. The mutation can result in a disorder known as genetic epilepsy with febrile seizures plus (GEFS+), which can present in different ways in different patients.
After the mutation was identified, the researchers then found it in fourteen other candidates. The lineages of the carriers was traced, and the researchers were able to follow the mutation back through generations, ultimately to one person. Next, the scientists looked for the mutation in the UK Biobank and found another 74 carriers. Patterns in the sequences of their DNA showed that the individuals were all carrying the same haplotype, which indicates a segment of DNA that has been inherited together, from one individual.
It is somewhat rare for an autosomal dominant, early-onset disorder to persist over many generations in this way, noted the researchers. They suggested that there are several reasons that explain this finding; the mutation only causes a mild disease, and in addition, it is not fully penetrant, so some carriers have an even milder case, and the disorder has not impacted their ability to have children in any way.
When an autosomal dominant mutation causes a particularly severe disease, it may be fatal to carriers before they reach an age where they are able to have children, or it might cause a survivable disease that nonetheless severely impedes a patient's ability or opportunity to reproduce. Mutations that cause severe disease typically get eliminated from a population for those reasons (unless they arise again spontaneously). The p.Cys121Trp mutation is not affecting carriers in this way.
However, the study authors noted that the mild phenotype that can be caused by this mutation may also mean that it is more common in the population than we know, and may be to blame for more cases of mild epilepsy than thought.