​​A new research article details the transformative effect that a programme by the Rare Disease Genomics in South Africa (RDGSA) research group has had on the lives of many people who have had to live with undiagnosed diseases for years.

The Undiagnosed Disease Programme (UDP) was established by the RDGSA to provide correct diagnoses to patients with rare diseases, and the group has recently published the results of their first year of operation in the American Journal of Medical Genetics. The RDGSA is situated within the Division of Molecular Biology and Human Genetics at Stellenbosch University's Faculty of Medicine and Health Sciences (FMHS).

The UDP is the first of its kind in sub-Saharan Africa and hopes to end the often soul-destroying “diagnostic odysseys" of undiagnosed patients with rare diseases. They use whole exome sequencing and whole genome sequencing to diagnose rare diseases.

In its first year, 100 patients took part in the UDP, and a diagnosis was reached in 51 of them.

“This represents a diagnostic yield of 51 percent. This is really encouraging, especially considering that this is the first programme of its kind in this region," said Professor Shahida Moosa, Associate Professor of Medical Genetics and head of the RDGSA group. “We have made such great strides in such a short time.

“These results show that the programme has already been transformative and potentially life changing as most patients have lived for years not knowing what disease they had. Most of them have had several rounds of tests, none of which delivered a diagnosis until we were able to use the latest in genomic technology, namely exome sequencing," she said.

Moosa said she was particularly thrilled that the paper is out in the American Journal of Medical Genetics.

“Also known as the 'blue journal', it is the leading journal for medical geneticists around the globe and it offers the paper open access to anyone working in the field," she said.

“It means that our peers who have had access for longer than we have to exome sequencing can see that the technology works just as well in our under-represented populations and that we too can show success employing this technology in our hospitals."

The RDGSA recruits patients and their families who are searching for diagnoses “to see if they would be good candidates for an exome sequencing test".

“We have offered it to several hundred individuals. The paper describes the success we have had in the first 100. In other countries where they have looked at similar cohorts, they have had diagnostic yields of between 30 and 35 percent.

“We have added a copy number variant analysis which brought us up to a 51 percent diagnostic yield. The families are so surprised and happy about this as they now have a name for the condition which their child has or which is running in the family for which they have not previously had a name," Moosa said. For some patients, they are the first in Africa to be diagnosed with their particular condition. She said the outcome of the work on the UDP has yielded rewards “way beyond my expectations".

“I really thought we would have trouble looking at and analysing the data as our patients come from populations which are under-represented and understudied. The results have however shown that we have the skills and ability to end the diagnostic odyssey in a way that is beneficial and gratifying for us."

Moosa said the programme is currently focusing on diagnosing paediatric patients in order to provide medical treatment and management at the most impactful time. “With time, we hope to include more adult patients. It is never too later to receive a diagnosis," she said.

“As the clinician and researcher who looks after the patients, I have watched how they have started off coming to me in the clinic with a big question mark on their faces; then how they have undergone testing in the lab and then how they have returned to the clinic to receive their diagnoses. For the patients, as well as their families, it has been extremely gratifying. And for me and my research group, even more so!"

Commenting on the fact that this is the first paper coming out of sub-Saharan Africa describing the clinical utility of exome sequencing in African patients, Moosa said: “When we apply for grants, people say things like Africa has other priorities like infectious diseases. I want to remind them that Africa also has people and families with rare diseases. Now we have the teams and the technology to diagnose people with rare diseases. We not only do it properly, but we also do it very well. 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. This programme is filling a gap we previously could not address."

Moosa said that the programme will soon be able to include many more patients. “A grant from the South African Medical Research Council will help us to do more sequencing for more families still waiting for a diagnosis. Recruitment is skyrocketing," she said.

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Caption: Prof Shahida Moosa and the rest of the Rare Disease Genomics in South Africa (RDGSA) research group.