In the largest study of its kind, researchers from the Wellcome Sanger Institute, Hinxton, found mutations in non-gene areas of the genome linked to rare developmental disorders of the central nervous system. These undiagnosed disorders can lead to conditions such as intellectual disability and epilepsy.
The genomes of nearly 8000 children and parents were analysed in the study, published in Nature, particularly focusing on noncoding DNA. While these sections are not translated into proteins, they can influence whether specific genes are switched on or off and so regulate their activity. The researchers demonstrated that mutations in these regions of the genome can cause neurodevelopmental disorders.
'For the first time, we've been able to say how many children with severe neurodevelopmental disorders have damaging genetic changes in parts of the genome called regulatory elements,' said Patrick Short, first author of the study. 'We're getting closer to providing a diagnosis for these families.’
To understand how specific non-gene mutations can cause neurodevelopmental disorders, the mutated regulatory elements have to be linked with the corresponding gene they influence. This can be difficult, as they are often located in different regions of the genome.
To do so will involve a larger study with more participants, but already 'this study is a promising step towards providing answers that families have been seeking for years', said Professor Anneke Lucassen at the University of Southampton, who was not involved in the study.
A minority of children with neurodevelopmental disorders are diagnosed based on their symptoms and the specific testing of genes known to be involved with these disorders. The wide range of symptoms, ranging from learning and behavioural problems to epilepsy and autism, make a precise diagnosis even more difficult.
This research is part of the Deciphering Developmental Disorders study, established in 2010 to analyse the genomes of 13,000 children with unknown developmental diseases. Findings, including the importance of non-gene mutations, may in the future allow more children to be diagnosed.