Q&A: Sofie Metsu on a newly discovered genetic cause of mental disability
Sofie Metsu, a PhD student at the University of Antwerp, has identified a new genetic cause of mental disability
Variation of fragile X syndrome
Which mental disability did you examine?
The disorder we studied is still unnamed, but you could see it as variation of the so-called fragile X syndrome. This syndrome takes its name from the mutation that causes it, which can be visible as a gap or break in the female sex chromosome. This “fragility” is caused by a so-called CGG-repeat expansion of the DNA: the bases corresponding to the letter sequence CGG are copied many times during cell division. As a consequence, the gene that normally sits on this spot of the chromosome is inactivated and thus cannot code for its corresponding protein. The fragile X syndrome is the most frequent cause of mental disability within families.
How did you discover this variation?
In our study, we focussed on a similar fragile site on chromosome 2. As it is the first fragile site of this type that was identified on the second chromosome, we termed it FRA2A. By studying the symptoms as well as the genetics in three afflicted families, we were able to identify this new genetic cause – or this new type of neurodevelopmental syndrome, if you will. However, in our case, the symptoms – slower development during childhood, mental disability – are much milder than in fragile X syndrome patients.
So how common is this syndrome?
That’s still unknown. The only thing we know is that it’s rare. We were only able to find three families in which the disorder occurs, thanks to our colleagues in Scotland and Australia. By way of comparison: the frequency of the fragile X syndrome, the most common fragile site associated disorder until now, is estimated to be only 1 in 5,000. The frequency of Down syndrome – in which the patient has three rather than two versions of chromosome 21 – is eight times higher.
Can faulty repetition of DNA on the other chromosomes also cause mental disorders?
Yes, that’s very likely. To date some 30 rare fragile sites spread across all 23 chromosomes have been reported in scientific literature. Until now, 11 of these have been molecularly characterised. And indeed, for seven of these a clear association with a neurodevelopmental disorder (autism, schizophrenia, intellectual disability) has been established.
