Clinical genetics

Quest: why more boys than girls with rare syndrome?

One thing stands out about children with the rare SETD1B syndrome. More boys than girls have the disease, and boys are more severely affected. Scientist Kristina Lanko is on a quest to discover what causes this sex difference. ‘Brain cells are my favorite cells.’

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Kristina Lanko
Kristina Lanko

Boys and girls with the rare SETD1B syndrome have many things in common: developmental delays, problems with talking and learning, behavioral problems, and sometimes epilepsy and autism. All have a defect in the SETD1B gene; that is the cause of the disease. But there are also differences. There are many more boys than girls with the disorder, and the behavioral problems in particular are more common in boys.

Erasmus MC researcher Kristina Lanko, is set out to get to the bottom of what causes this sex difference. To do this, she is going into the laboratory. Lanko takes skin cells from male and female patients and turns them into stem cells. Using what she calls “a few magic tricks”, she transforms the stem cells into different types of brain cells. Lanko is a postdoc in the laboratory of Stefan Barakat at the Clinical Genetics Department.

First in her field

Lanko hopes to find differences between the male and female stem cell derived brain cells. ‘For example, we’re looking at which genes are expressed, because we know that the SETD1B protein affects gene expression. We are also looking at how well the neurons pass on signals to each other. Do they still function well as a network?’

Lanko will also make pools of mini-brains from the patient cells to study “patients-in-a-dish”. A first in her field. ‘We add the stem cells from different patients together and let them grow into a brain organoid. In doing so, we mimic the early stages of brain development.’ Each cell has its own role in the brain organoid and can be traced back to an individual patient through the unique genetic signature. In this way, Lanko hopes to find out what goes wrong in which patient.

Favorite cells

Lanko can’t wait to get started. ‘Brain cells are my favorite cells. Just because of their sheer beauty it’s fantastic to work with them. Moreover, they are the cells that make you human. That makes this project beautiful: I know that behind every cell there is a person.’

About the SETD1B syndrome

  • Patients with SETD1B syndrome have delayed development, often in combination with behavioral problems and epilepsy
  • The condition is caused by a defect in a gene called SETD1B
  • The SETD1B syndrome is rare. A 2021 international study, led by Erasmus MC, describes 36 patients worldwide. The exact number of patients is unknown.
  • The syndrome is more common in boys than girls, and boys tend to have more symptoms. The reason for this is not yet known.
  • There is no treatment that can cure SETD1B syndrome.

This project is made possible by a 148.510 euro contribution by ZonMw (PSIDER Doorbraakprojecten grant).

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