{"id":135061,"date":"2022-01-21T14:14:44","date_gmt":"2022-01-21T13:14:44","guid":{"rendered":"https:\/\/www.erasmusmagazine.nl\/en\/?p=135061"},"modified":"2025-12-19T11:26:05","modified_gmt":"2025-12-19T10:26:05","slug":"stefan-barakat-when-the-zebra-fish-developed-epilepsy-the-cause-was-clear","status":"publish","type":"post","link":"https:\/\/www.erasmusmagazine.nl\/en\/2022\/01\/21\/stefan-barakat-when-the-zebra-fish-developed-epilepsy-the-cause-was-clear\/","title":{"rendered":"Stefan Barakat: ‘When the zebra fish developed epilepsy, the cause was clear’"},"content":{"rendered":"

Stefan Barakat is searching for the genetic cause of neurological developmental disorders in a relatively unknown part of the DNA and on 14 February will receive a prestigious incentive award, the Early Career Award, for his research. \u201cWe\u2019re searching for spelling errors in DNA.” <\/p>\n

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\n\t\n\n<\/svg>\n<\/span>\n\tImage by:<\/span>\n\n\t\t\t\n\t\t\t\t\t\t\tWouter Sterrenburg<\/a>\t\t\t\t\t<\/span>\n\t<\/p>\n<\/figcaption><\/figure>

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. <\/p>\n

You\u2019re working in a lab, and you\u2019re a physician. How do you combine that?<\/strong><\/p>\n

\u201cI\u2019m 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.\u201d <\/p>\n

How large is the group of patients with these rare disorders?<\/strong><\/p>\n

\u201cIt\u2019s quite large, so it\u2019s 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\u2019re 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\u2019ve often already undergone a long odyssey through various medical specialists. And despite all our progress, we\u2019re not always able to make a diagnosis. We want to improve that.\u201d <\/p>\n

What do you do exactly as a genetics researcher?<\/strong><\/p>\n

\u201cOur 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\u2019s DNA to a chapter of a book. If there\u2019s a spelling error somewhere, this can change the meaning of the book. Some twenty thousand genes in DNA code for proteins. That\u2019s the part we know. But that\u2019s just 2 per cent of all DNA. We actually still know very little about the remaining DNA.\u201d <\/p>\n

What is new about your research?<\/strong><\/p>\n

\u201cWhen 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\u2019re using advanced computer technology and lab techniques to try to trace these switches and test the effect of these switches on genes. We\u2019re 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\u2019s causing their symptoms, and this can also be significant for their treatment. <\/p>\n

\u201cFor 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.<\/p>\n

\u201cSuch 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\u2019t 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.\u201d<\/p>\n

Zebra fish?<\/strong><\/p>\n

\u201cThese fish are transparent in their embryonic stage, so you can see what\u2019s happening in the brain. When the zebra fish developed epilepsy after we\u2019d 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\u2019s a condition now known as Barakat-Perenthaler syndrome, as our lab discovered it. <\/p>\n

\u201cUsing our network and an international database for genetic researchers, we\u2019ve 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. <\/p>\n

But how could someone from in Baluchistan have reproduced in Westland that many hundred years ago?<\/strong><\/p>\n

\u201cThe 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. <\/p>\n

Fascinating. The KNAW jury described you as a bridge builder. What does the jury mean by that?<\/strong><\/p>\n

\u201cWe try to convert our findings into therapy, and we\u2019re 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\u2019re building bridges between patient care, diagnostics and research, both locally and internationally.\u201d <\/p>\n\t

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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. <\/p>\n\n\t<\/div>\n\n\t

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