Approved Research

The genetic landscape of idiopathic neurodevelopmental disorders and in the Middle East and risk modulation by ancestry

Lay summary

Neurodevelopmental disorders (NDDs) are a group of complex conditions that impact the natural development of the brain in growing children causing intellectual disability, in addition to motor, learning and sensory deficits. Although some of the adverse symptoms of NDDs can improve over time with therapy, certain are more permanent and persist long-term. Epilepsy, often occurring alongside NDDs, is the most frequent and disabling form of neurological disorders in young children. Further to compromising the child's quality of life, NDDs and epilepsy constitute a significant liability to society as well as the healthcare system.

There are specific types of NDDs such as the Coffin-Siris syndrome for which the genetic cause is already well characterized; yet in many cases, the cause remains unknown. Recent advances in deep genome sequencing have made it possible to compare the DNA sequence of affected children to their normal parents and pinpoint newly emerging changes in the child's DNA that are likely to be causative of the impaired phenotype. For certain complex types of NDDS including autism as well as generalized epilepsy, scientists suspect an interplay between a multitude of genetic factors collectively contributing to the adverse outcome. These factors can be screened for by analysing the genome-wide alternations in DNA in a suitably sized cohort of affected subjects.

Pinpointing the dysfunctional gene(s) at the early stage of child development can be tremendously helpful for tailoring a suitable therapy that can reduce the severity of the symptoms long-term. Over the next coming years, we aim to explore sequencing and phenotypic data at the UK Biobank as well as families with affected children, recruited at our end, to determine the genetic factors that increase the susceptibility to NDDs and neurological epilepsy. We will be looking for genetic risk factors that are prevalent amongst Qataris owing to the country's high rate of interrelated marriages and we will compare them to those that are more evident in the UK Biobank cohort. We will seek to delineate collective genetic risk patterns, or variations in DNA that tend to occur together, in subsets of affected individuals. By grouping patients with similar genetic defects, we shall be empowering doctors to advise on each group's most suitable treatment.