Antwerp researchers identify autism gene
A 25-year-old PhD student from Antwerp has stumbled upon a gene that can cause autism in the case of mutations
Mutation just “pops out” in patients’ genomes
But in a ground-breaking discovery earlier this year, scientists from the University of Antwerp and the Antwerp University Hospital (UZ Antwerp) identified an entirely new genetic cause of ASDs. Intriguingly – and maybe also a bit frighteningly – they identified a series of genetic mutations that aren’t hereditary; they just happen to “pop out” in the DNA of unlucky children. Geneticists call these mutations de novo; this means that they originate in the child. The discovery was described in the science and medicine journal Nature Genetics last month.
ASDs are developmental disorders that are characterised by social deficits, communication difficulties, repetitive behaviour and thoughts and, in some cases, a certain degree of cognitive delay. While ASDs were once considered to be consequences of youth traumas or other challenges experienced during childhood, scientists have now established that social or psychological factors don’t play any part. ASDs are fundamentally biological and occur as a result of problems during the development of the brain.
But biological isn’t the same as hereditary – just like genetic doesn’t always mean that you get it from your mum or dad. There are indeed some environmental factors that can cause ASDs, like certain viral infections, illness of the mother during pregnancy, oxygen deficiency during birth and long-term exposure to heavy metals.
These environmental factors cause problems during brain development, and they account for roughly 10% of all the causes of ASDs. The other 90% is purely genetic.
The most common genetic causes of ASDs are the so-called Fragile X syndrome (when there’s a mutation of the female sex chromosome), tuberous sclerosis and (in 5 to 7% of cases) children with Down syndrome. Some of these known genetic defects are hereditary, with parents likely to transmit the disease to their children.
Next generation sequencing
The recent research was mainly carried out in the medical genetics department at UZ Antwerp. Céline Helsmoortel is working on her PhD, in which she uses a new technology – dubbed “next generation sequencing” – to investigate new causes of intellectual disability and autism. All the new mutations were found in the gene that codes for the activity-dependent neuroprotective protein (ADNP). She stumbled upon the mutation in the ADNP gene while examining the DNA code of two patients at the hospital with a severe form of ASD.
It had to be a rare mutation – otherwise it would have been discovered much earlier
“This gene immediately caught my attention,” Helsmoortel explains, “because it plays an important role in the development of our brain, in learning and memory processes.” But the 25-year-old student only had two patients – not a good basis for a sound statistical estimation of a causal relationship between the mutation and this specific type of ASD.
Helsmoortel: “That this was a de novo mutation gave me hope. Every one of us has around 10 of these mutations in our genes. So it definitely had to be a rare mutation – otherwise it would have been discovered much earlier.”
Helsmoortel searched and found international assistance. With help from colleagues from the Netherlands, Sweden, Italy, Australia and the US, she was able to find eight other patients with the same clinical background (the same symptoms of this form of ASD). In each of their genomes, the international researchers were able to identify mutations in the ADNP gene.
“Because we found it in every one of our 10 ASD patients with these particular symptoms, it was clear for us that there was indeed a causal relationship,” says Helsmoortel.
So how important is the discovery of these new ASD-causing mutations? Helsmoortel explains that they looked for mutations in this same gene in 5,776 patients (including the hospital’s 10 patients) who were also diagnosed with ASD. “Again, our 10 patients ‘popped up’ as the carriers of mutations in this gene. This means that in 0.17% of all the people with ASD, their disease is caused by a malfunctioning ADNP gene. That’s much less than with other genetic causes, but what’s special about this one is that the mutation is de novo – it just popped out in the patient’s genome – somewhere during embryo development.”
So does this mean that these patients – unlike their parents – are actually able to transmit ASD to their children? “In theory: yes,” she says. “But in practice they are so severely affected that they probably won’t have children. So the mutations will mostly disappear again. That’s also why it’s so rare.”
Thanks to the discovery, doctors can now more easily diagnose ASD. Indeed, like the spectrum element in the name of the disorder indicates, a foolproof diagnose of ASD isn’t always possible – the range of symptoms is often too broad. However, says Helsmoortel, “if you see a mutation in the ADNP gene, it’s definitely the cause of the ASD.”
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