Rare Disease Genomics
Welcome to Stellenbosch University

Division of Molecular B​iology and Human Genetics

Rare Disease Genomics


Under the umbrella of “Rare Disease Genomics in South Africa”, we use the latest in state-of-the-art “omics” and next-generation sequencing technologies to study African patients with genetic rare diseases. We are particularly fortunate to be able to offer African patients access to this technology, as they are understudied and under-represented in genomics worldwide.
Our projects include:

  • The Undiagnosed Disease Programme (UDP) – this is the first UDP in sub-Saharan Africa. We use whole exome sequencing and whole genome sequencing to find diagnoses for undiagnosed patients with rare diseases. Our current focus is on diagnosing paediatric patients as soon as possible, to be able to change medical treatment and management at the most impactful times. With time, we hope to include more adult patients. It is never too late to receive a diagnosis! The results from the first year of the UDP have just been published in the American Journal of Medical Genetics Part A - of the first 100 patients, a diagnosis could be reached in 51 (a diagnostic yield of 51%). This is very encouraging, and shows that even in this understudied population of patients with rare diseases, exome sequencing has definitive utility. For this large project, we are also building and optimizing the bioinformatic pipelines - we are particularly interested in students and postdocs who are keen to contribute to this effort - please email shahidamoosa@sun.ac.za 

  • Next Generation Phenotyping using Artificial Intelligence - please see our GestaltMatcher paper​ in Nature Genetics for work done in collaboration with the expert team of Prof P Krawitz at the University of Bonn in Germany. If you're interested in joining the GMDB​ (GestaltMatcher Database community), please contact us. Read more about GMDB here
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  • Elucidating the genomic causes of Skeletal Dysplasias in South Africa using Next Generation Sequencing approaches - this project aims to identify existing or novel causal genes and variants underlying skeletal dysplasias in South African patients. Skeletal dysplasia is an umbrella term that encompasses over 400 skeletal disorders, each with varying levels of severity. Although a clinic-radiological diagnosis is possible in many skeletal disorders, we have increasingly appreciated the profound impact of having a definitive molecular genomics diagnosis to guide treatment and management. 
  • Genetics of Epilepsy in Africa - Epilepsy is the most common manifestation of neurological disease and the burden of epilepsy in Africa is significant. In children the prevalence of epilepsy is highest in the 1st years of life, and a genetic underlying cause is most often implicated.  We conducted one of the first studies in Africa to determine the clinical utility of genetic testing in children with early onset epileptic encephalopathy.  Using a next-generation-sequencing approach, we are able to provide almost half of our little patients with a diagnosis (paper accepted at Seizure).  Early diagnosis and early treatment have a better impact on future cognitive and behavioural development. In addition, the genetic result plays a role in guiding physicians to decide on the type of anti-convulsant medication. Crucially, a definitive genetic diagnosis provides accurate inform​ation to parents on aetiology of the epilepsy and provides information for reproductive counselling for future pregnancies. There is paucity of data in Africa regarding epilepsy genetics and the genetic architecture underlying early onset epileptic encephalopathy in the African population. ​
  • HMPRS in South Africa: investigating a common variant in PGAP3 - Hyperphosphatasia with mental retardation syndrome (HPMRS) is a rare autosomal recessive disorder associated with glycosylphosphatidylinositol biosynthesis defects, which, result in intellectual and physical disabilities. This project focusses on the identification of a novel variant in the PGAP3 gene among Xhosa HPMRS patients. Currently, we are investigating if this variant is a founder mutation for HPMRS in the South African isiXhosa population.
  • Diagnosis of copy number variations using array-based comparative genome hybridisation in fetuses and neonates with congenital abnormalities in a South African population - Genome-wide assessment of copy number variations (CNVs) is recommended by numerous groups as a first-tier genetic test for the prenatal evaluation of fetuses with structural abnormalities detected on ultrasound and for neonates with unexplained multiple congenital abnormalities (MCA). Chromosomal microarray (CMA) is more commonly being utilized in prenatal and neonatal diagnosis due to its improved detection rate of clinically significant chromosomal abnormalities. This study aims to investigate the incidence of CNVs detected in fetuses with abnormalities on ultrasound and neonates with MCA in the South African population, in the hope to increase the diagnostic yield of genetic disorders using CMA.
There are many more projects available, spanning clinical genomics, bioinformatics and molecular genomics as well as wet-lab molecular biology. Interested students and postdoctoral fellows as encouraged to contact Prof Moosa (shahidamoosa@sun.ac.za) to discuss possible projects.


Along with international collaborations which have facilitated the research, Prof Shahida Moosa was recently awarded the SAMRC Early Investigator grant. This funding, totalling R2.5million, will go a long way to helping more families access genomics, and will primarliy support sequencing costs for the Undiagnosed Disease Programme.

Read more about the award here
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