More than four dozen new gene mutations linked to autism and other child development disorders have been discovered by British scientists.
They say the breakthrough could lead to better treatments for a range of conditions – including ADHD (attention deficit hyperactivity disorder).
They affect the acquisition of specific skills such as attention, memory, language and social interaction.
Although they have a genetic cause, this is often difficult to detect as the variant do not appear in either parent.
Known as DNMs (de novo mutations), they can be important in autism, ADHD, intellectual disability and Rett syndrome that impairs speech and breathing.
The study is the largest of its kind and was based on an analysis of the complete DNA of more than 31,000 ‘parent-child trios’ in the UK and the Netherlands.
It identified 49 previously unknown genes linked to autism and other severe developmental problems.
There are an estimated 700,000 Britons with some kind of autistic disorder – more than one in 100 people. There is no cure.
The results, presented at a meeting of the European Society of Human Genetics in Gothenburg, Sweden, offer hope of earlier diagnosis.
They could also lead to the development of gene therapy drugs that prevent or combat symptoms.
Lead author Joanna Kaplanis, a PhD student at the Wellcome Sanger Institute in Cambridgeshire, said: “Although many new developmental disorders have been identified in recent years, there are many more to be discovered.
“Identifying them means we will be able to give an accurate diagnosis to more patients and therefore allow them to have appropriate treatment and care.”
Overall, her team discovered more than 45,000 DNMs. Using an improved testing technique, they narrowed these down to the most damaging that were over represented, or ‘enriched’, in the sample.
Ms Kaplanis said: “We found 307 significantly enriched genes, 49 of which are novel. With all of these genes we were able to explain about 51% of the DNM burden in our dataset.
“We then modelled different underlying genetic scenarios to get an idea of where the remaining de novo burden lies and how we can go about finding it.”
About four in ten developmental disorders are caused by DNMs, equivalent to about one birth in every 295 in the UK alone. The prevalence increases with the age of the parents.
Usually becoming apparent during childhood, in many cases those affected will need lifetime support.
But when they are unidentifiable making a decision on the best care for the patient is difficult.
Given the size of the dataset, the researchers were not surprised to have been able to identify so many new genes.
But Ms Kaplanis said: “However, we were expecting to be able to explain more of the DNM burden than we did.
“This means that half of the DNM burden in patients with developmental disorders still remains unexplained.
“This fact alone gives us clues about where the remaining burden lies and why we do not yet have the capacity to discover the remaining genes.”
One possibility is the DNMs in the genes as yet undiscovered trigger symptoms in fewer people.
Ms Kaplanis said: “We may need to adapt our system of gene discovery in order to capture these less penetrant genes.
“Incorporating more data from healthy populations may help to try and build a better picture of what they might be.”
The researchers also hope to increase their sample size in order to try to detect ever more genes associated with developmental disorders.
But the identification of the new genes already provides valuable information to clinicians and to drug developers.
Ms Kaplanis added: “Returning a genetic diagnosis is important when deciding on the best treatment and care for an individual, as well as providing new drug targets in rare diseases.”
In the UK, it is thought up to one in twenty children may have ADHD. Previous research has suggested there are about 1,000 genes linked to autism.
Conference chair Professor Joris Veltman, director of the Institute of Genetic Medicine at Newcastle University, said: “Developmental delay is often caused by new mutations arising during the formation of sperm or eggs.
“By combining data on new mutations identified in the DNA of more than 30,000 patients, the scientists could implicate a role for 49 new genes in developmental delay.
“This study shows the power of large-scale international collaboration to advance our understanding of this disorder and improve diagnostics as well as patient management.”
