A Brunel University London professor has joined the illustrious pantheon of Hans Asperger and John Langdon Down by having a syndrome named after her. Professor Alex Blakemore, head of Brunel's Department of Life Sciences, received the unusual honour after a new study described and named a rare form of obesity that was first identified by her team in 2016.
Blakemore-Durmaz-Vasileiou syndrome (BDV), named after Blakemore, Dr Asude Durmaz from Turkey's Ege University and Dr Georgia Vasileiou from Germany's Erlangen University, is a rare genetic disorder that presents itself through a complex range of symptoms, including delayed cognitive development and an uncontrollable appetite. The specific genetic variants found in those who have the syndrome were first identified by Blakemore in 2015, after she was approached by a clinician whose patient was exhibiting a mysterious array of symptoms.
"I have been working for much of the last 10 years to explore the genetics of extreme obesity," said Blakemore. "Most people do not realize that some forms of obesity run in families just like other inherited disorders, such as cystic fibrosis or Huntington's disease."
Blakemore and her team studied the DNA of a young woman who had learning difficulties, diabetes, problems with reproductive hormones, and severe, uncontrollable hunger sensations, and whose brother had passed away in young adulthood exhibiting very similar symptoms.
"The family had already been investigated for other potential causes, including Prader-Willi syndrome [which has similar symptoms to BDV], so it was a mystery," said Blakemore, who was asked by the clinician to perform DNA sequencing on the patient. "In this case, the parents were cousins, which meant that there was an increased chance of the patient having inherited two copies of the same harmful genetic variant. This makes the potential problem easier to identify, so we decided to give it a try."
The genetic sequencing revealed that Blakemore and her colleagues had discovered something new. Whereas Prader-Willi syndrome (named after Swiss physicians Andrea Prader and Heinrich Willi and thought to affect up to 30,000 people worldwide) is caused by a faulty chromosome 15 that has been inherited from the father, BDV is caused by a much smaller change to a single gene.
As the parents were closely related, the patient in Blakemore's case had inherited the damaged genes from both her mother and her father, resulting in them being unable to produce the enzyme carboxypeptidase-E (CPE), which plays an important role in regulating appetite, as well as other body systems.
"This explained why she was so hungry all the time," said Blakemore.
In the years following Prof Blakemore's discovery, further children were identified with the same symptoms, amongst which were patients whose conditions have now been described in detail for the first time in the paper, ‘BDV Syndrome: an Emerging Syndrome With Profound Obesity and Neurodevelopmental Delay Resembling Prader-Willi Syndrome’, published in The Journal of Clinical Endocrinology and Metabolism.
"Not surprisingly, all the affected patients in our study were initially suspected to have Prader-Willi syndrome," said Dr Georgia Vasileiou, a Resident in Clinical Genetics at Erlangen University in Nuremburg. "Nevertheless, molecular analysis excluded the genetic defects underlying Prader-Willi syndrome."
After identifying genetic damage in the patients using a powerful method known as "exome sequencing," Vasileiou and her colleagues scoured anonymised genetic databases to see if others with the same damage had previously been found.
"In her study of 2015, Professor Blakemore described the first individual with obesity, developmental delay, and diabetes, carrying a genetic defect in the CPE gene," said Vasileiou.
"Comparing the clinical characteristics of our patients with her affected individual led us to conclude that all these individuals had the same disease. Importantly, with a total number of eight described patients we were able to define Blakemore-Durmaz-Vasileiou as a syndrome with distinct clinical and genetic characteristics."
On entering the pantheon of eponymous syndromes, both Blakemore and Vasileiou said it was gratifying to receive the recognition of having something named after them, and that they're pleased their patients are now in a better position to understand their condition.
"It feels a little odd to have a medical condition named after me specifically, particularly when other people such as my PhD student at the time, Dr Sanne Alsters, played such big roles in this too," said Blakemore, who continues to work on rare inherited forms of obesity and diabetes.
"On the other hand, as a scientist and a human being I think we all want to make some positive difference in the world. In this case, the patient was able to receive a diagnosis, which provided the family with an explanation for their difficult situation, and a way forward in terms of genetic counselling if they want that. It feels good to know that, as well as adding to our knowledge of inherited obesity syndromes, my team's work has had a real-life benefit."