Problem Statement
Few studies about genetic of neurodevelopmental disorders have been conducted in Sub-Saharan Africa and the genomic information underlying their mechanisms, especially in Rwanda, is still not adequately available. This study will focus on identification of genetic and environmental factors to better understand and mitigate the prevalence and impact of NDDs in the region.
Progress Highlights
The key activities accomplished under these project goals include Collecting blood and serum samples from 233 participants, extracting DNA from the blood samples of all participants, capacity building for PhD and master’s students and laboratory technicians (basic genomic skills, karyotype analysis), submitting one article for peer review, and holding collaborative monthly meetings among team members.
Key Findings
Whole exome sequencing (WES) of 18 patients with dysmorphic features and neurodevelopmental disorders (NDDs) was conducted. Thirteen pathogenic or likely pathogenic variants were identified in 13 patients, and variants of uncertain significance (VUS) were identified in 5 patients. For each case in the cohort, we compiled frontal photos, clinical features, and the disease-causing variants. The diagnostic yield of WES for dysmorphic features and NDDs was 72.2%.
Potential Impact
We conclude that the association of dysmorphic features and developmental delay in patients with neurodevelopmental disorders can predict the likelihood that whole exome sequencing (WES) will identify a causal variant of a phenotype. Therefore, systematic use of WES in NDDs will improve the diagnostic yield of rare diseases and enable better management.
Summary
Genetic and environmental risk factors causing many cases of neurodevelopmental disorders in Africa are generally unknown. Neurodevelopmental disorders occur when complex genetic and environmental factors combine to change brain development. In children, these disorders are usually characterized by impairment in intellectual functioning, reading ability, social skills, memory, attention or focus skills.
Dr Uwineza’s research will use advanced genetic laboratory technics to identity changes in patients’ DNA associated with neurodevelopmental disorders, autism spectrum disorders and microcephaly.
Grantee Description
Dr Annette Uwineza is a Senior Lecturer in the Department of Clinical Biology at School of Medicine and Pharmacy of the College of Medicine and Pharmacy at the University of Rwanda. She obtained her PhD in Medical Sciences (Human Genetics) from the University of Liege (Belgium) in 2015 and her doctoral work focused on identifying the genetic aetiologies of intellectual disability in Rwandan patients.
Dr Uwineza’s long aspiration is develop and expand genetic testing in Rwanda population to allow affected families getting genetic diagnosis required to get information about long-term needs, and future family planning.
Project: Genomic and Environmental factors of neurodevelopmental disorders in Rwandan Children
The goal of this project is to identify genomic and environmental factors associated with neurodevelopmental disorders by perfoming whole exome sequencing in affected children, genome wide association studies in patients with Autism Spectrum Disorders, then to investigate the infectious and genomic etiology of microcephaly in Rwandan newborns. Our project’s results will alert regional public health stakeholders who may use the information to implement or reinforce existing measures of prevention of microcephaly.
In addition, this project will also allow to develop appropriate assessment tool that suits Rwandan and African system to gather relevant information on various risk factors associated with neurodevelopmental disorders.
