Two to three percent of the population has a developmental disorder, such as autism or an intellectual disability. More than 1,800 genes are now known to cause developmental disorders.
In about 40% of cases of developmental disorders, these are accompanied by other physical or facial characteristics and are therefore recognizable as syndromes to doctors and other professionals. However, the majority of children with a developmental disorder do not exhibit any additional recognizable characteristics.
Children with variants in the ELAVL2 gene
“The absence of these additional characteristics makes it difficult to identify new genes associated with these developmental disorders and, consequently, to perform genetic testing,” says Dr. Bert de Vries, a clinical geneticist and leader of the study. Five years ago, during his clinic hours at Radboudumc in Nijmegen, De Vries saw a 3-year-old boy who was diagnosed with a mutation in the ELAVL2 gene. “At the time, this was not known to be a disease-causing gene,” De Vries continues. “However, through international collaboration, we assembled a group of 16 children with mutations in the ELAVL2 gene.”
Jolijn Verseput, a physician-researcher and Ph.D. candidate, then set out to compile as many clinical characteristics as possible from this group of children. “All the children had a developmental disorder, and some had autism, sleep problems, epilepsy, difficulty processing sensory input, and emotional instability,” she explains. However, no additional distinctive physical characteristics were observed, as is the case with other well-recognized syndromes. “Is this genetic variation actually the cause of these symptoms?” Verseput wondered.
Fly model helps
Here, they enlisted the help of Prof. Annette Schenck’s fly research group. “We have a lot of experience creating fly models based on genes found in both fruit flies and humans.”
Marina Boon, then a Ph.D. student in her group, got to work. “We knocked out the ELAVL2 gene in the fruit fly and then examined what effect this had on the fly and its behavior,” says Boon. “We observed that these flies had an increased susceptibility to epilepsy, difficulty processing sensory stimuli, and sleep problems,” she continues. “In short, this closely matched what we had previously observed in children with this genetic abnormality.”
In collaboration with a research group in New Zealand, it was also demonstrated that the mutated gene resulted in a malfunctioning protein.
A long journey
After five years of research, it has now been proven with certainty that the mutation in the ELAVL2 gene in the boy, who is now 8 years old, was indeed the cause of his symptoms.
“These new insights enable us to better support him and the other children and to treat them where possible,” concludes De Vries. “And, of course, it’s another step forward in our understanding of the causes of developmental disorders.”
