Assistant professor Stefan Barakat (1984) is a physician in training to become a medical specialist at Erasmus MC in the Clinical Genetics department. He is conducting brain research in a lab together with an international network of geneticists.

You’re working in a lab, and you’re a physician. How do you combine that?

“I’m researching extremely rare inherited conditions of the brain and I also treat patients for this. So, the two overlap. I also manage a lab of ten researchers.”

How large is the group of patients with these rare disorders?

“It’s quite large, so it’s also a huge problem. On average, some eight thousand patients a year arrive at our department, and around a third of them have some kind of brain disorder. Many of the inherited conditions they’re suffering have a huge impact, including learning impairments, which have a major effect on the people affected and their families, as well as involving high care costs. Before patients arrive with us, they’ve often already undergone a long odyssey through various medical specialists. And despite all our progress, we’re not always able to make a diagnosis. We want to improve that.”

What do you do exactly as a genetics researcher?

“Our specialist field is relatively young, and a lot of what we think we know about genes, inheritance and DNA is still developing. You could compare a person’s DNA to a chapter of a book. If there’s a spelling error somewhere, this can change the meaning of the book. Some twenty thousand genes in DNA code for proteins. That’s the part we know. But that’s just 2 per cent of all DNA. We actually still know very little about the remaining DNA.”

What is new about your research?

“When diagnosing disorders, many researchers and practitioners look only at genes and not at the other 98 per cent of DNA. Research has shown that there are extremely important elements in that remaining DNA, so-called enhancers or switches that can switch genes on or off. We’re using advanced computer technology and lab techniques to try to trace these switches and test the effect of these switches on genes. We’re also interested in genes that were not previously linked to a condition, so we can check whether anomalies in these could cause disorders in those patients where we are currently unable to make a diagnosis. Together we hope to find an answer for what’s causing their symptoms, and this can also be significant for their treatment.

“For instance, a child from Westland with a rare form of epilepsy ended up in our department a while ago. She was having an attack every ten minutes, and her brain could hardly develop. Unfortunately, the child only reached the age of three.

“Such serious forms of epilepsy usually have an inherited cause, which is why we wanted to know how this genetic disorder worked. No known cause was found during routine diagnostics, but we did find a variant in a gene that wasn’t yet linked to a disease. In this case, both parents carried this same spelling error in the gene; an error that resulted in the supply of sugar and protein to the brain being blocked. We were able to recreate this anomaly in zebra fish.”

Zebra fish?

“These fish are transparent in their embryonic stage, so you can see what’s happening in the brain. When the zebra fish developed epilepsy after we’d introduced that same spelling error found in the child, we knew that this spelling error was the reason she was so ill. We knew for sure that the defect in the gene was causing those children to develop epilepsy. It’s a condition now known as Barakat-Perenthaler syndrome, as our lab discovered it.

“Using our network and an international database for genetic researchers, we’ve now found over forty children with this condition worldwide; all with the same anomaly. Through genealogical research we discovered that all patients had the same ancestor who must have lived some 600 years ago, probably in Baluchistan, an area in present-day Afghanistan, Pakistan and India.

But how could someone from in Baluchistan have reproduced in Westland that many hundred years ago?

“The East India Company used to sail to a trading post in those parts at the time. Probably someone embarked in Rotterdam, had children with a descendant of that common ancestor and travelled back to the Netherlands with the child.

Fascinating. The KNAW jury described you as a bridge builder. What does the jury mean by that?

“We try to convert our findings into therapy, and we’re now investigating whether we can develop drugs to treat this rare and related less rare forms of epilepsy. This ensures that our research enhances diagnostics and vice versa. And we can swiftly present our findings to the patient. We’re building bridges between patient care, diagnostics and research, both locally and internationally.”

The Early Career Award is being presented for the third consecutive year on 14 February by the scientific association, the Royal Netherlands Academy of Arts and Sciences (KNAW). There are twelve Dutch winners this year and two are from Rotterdam: sociologist Jonathan Mijs and medic Stefan Barakat. The EUR researchers will receive an artwork and 15,000 euro.