Looking to the future with Professor Shahida Moosa

Photograph by Annie Spratt, Unsplash

Africa is one of the most genetically diverse continents, and the African human genome is the oldest, yet fewer than 3% of analysed genomes come from the region. This low level of analysis brings many problems, not least the fact that not all research that has focused on the Caucasian population will have the same validity for this region. However, it does also provide opportunities, as Professor Shahida Moosa, Specialist Consultant in Medical Genetics (Tygerberg Hospital) and Associate Professor of Medical Genetics (Stellenbosch University) explained:

“To date, priority has focussed on diseases such as tuberculosis, HIV and infectious diseases. It has meant that historically there has been very little buy-in from the government and other stakeholders to develop the genetic diagnostic and research capabilities, especially with regards to rare diseases, it is hoped that this is slowly changing.”

“Currently, South Africa has nine provinces and there are only genetic services in two of those. These centres are the only locations that are carrying out diagnostics and research, yet there is a population of approximately 59 million in South Africa. It is estimated that within the population, there are possibly 4 million people with rare diseases in the community that need help, both in terms of diagnostics and research. This demand is putting huge strains on small teams who also have to cope with an already overloaded clinical workload.”

All humans descended from our shared ancestors who lived in Africa over 150,000 years ago. Each person carried part of the ancestral genetic variation, and through migration the genetic variants seen outside of Africa tend to be subsets of the genetic variants found in Africa. Over time as we reproduce the ancestral chromosomes get broken up and shuffled through recombination events over each generation. However, some segments of DNA are not fragmented and are shared between multiple individuals. These segments are called haplotypes and can be used to look for genes associated with a specific disease. The fact that genetically people descend from Africa means that many people share a disease haplotype no matter where they live now. On the whole European populations are genetically similar and the higher levels of analysis have meant there is a much larger data set. However, the African population is much more diverse and therefore the data from Europe is unlikely to cover genetic variants found in African populations. It is this demand for greater understanding that drives Professor Moosa;

"I grew up and trained in Johannesburg and after becoming a doctor I became a clinical geneticist, the first person to do the primary specialty in medical genetics. I realized that whilst clinically I was confident, I needed more experience on the research side because we just did not have the resources. I went to Germany and obtained my PhD and this was followed by a postdoctoral at Boston Children’s Hospital in the United States. The opportunity then arose at Tygerberg Hospital and I realised I could make a positive difference here. The university has supported me in setting up a lab where we can do rare disease genomics and I’ve also established our first undiagnosed disease program at Tygerberg Hospital, which started at the beginning of last year. This is the first UDP in Sub-Saharan Africa. Doing clinical genetics in African patients is a challenge to us because many of the big studies that have looked at normal variation across populations didn’t consider Africa. This means that when we find something, we don’t know how to interpret it. There’s nothing that can help us."

We have already enrolled 300 families and begun or conducted exome sequencing on 250 of them. Even in this short time, we have been able to diagnose half of them which is incredible. Getting a diagnosis is life-changing for many.

Professor Moosa

Photograph by Tebogo Masilela,Unsplash

It is incredible to see the difference it makes to someone’s life.

Professor Moosa

There are many issues associated with having a disability and rare disease and to be able to give them a name for their condition empowers people to share the information in their communities. Historically there has been a stigma to being different and some felt it was their fault their children had a rare disease. Even today there are superstitions associated with disease;

“To receive a diagnosis and to be able to say ‘my child has X Syndrome, this is genetic. It is not something that I ate during pregnancy, it’s not something that somebody did to me. It is in the building blocks of our bodies. One of my patients has been waiting 7 years for a diagnosis. We have been able to identify their condition and through this, they have secured a house in a new development specifically for people with special needs. Without a diagnosis, they could not have accessed it. It is incredible to see the difference it makes to someone’s life.”

“Covid has brought some positives because we have had sequencing machines donated. I am working with other partners across the world to be able to set that up as a test for us, not only for South African patients but to serve the rest of Africa as a hub to do genomics, in Africa for African patients. I am really excited and a little daunted by the amount of work that’s coming our way. I do believe that it is exactly why I was put here at this time, in this space.”

Recognising that the impact of a rare disease diagnosis is not solely constrained to the medical world but that it also has a huge impact on social interaction, education and employment is so valuable. On Rare Disease Day this year Professor Moosa and her team set out to ask the question ‘What is it like getting a diagnosis? What does this mean for you, what has or has not changed?’ This information is so important in reflecting the wider implications of diagnosis and highlighting the importance of research.

When I give a diagnosis, I always emphasize that this is not the end of their journey. In many ways it is the start.

Professor Moosa

Photograph by Annie Sprat, Unsplash

“By understanding the true impact of a diagnosis on people such as parents, caregivers and people inside in the community, it allows us to recognize where they need support, what has worked, what hasn’t worked, what are the challenges that they face, and how we can help to overcome those challenges.”

It is one thing to be increasing the testing capability but if there is not sufficient understanding about how to interpret that data then errors will occur. Professor Moosa is passionate about improving understanding, not just amongst clinicians but also among medical students.

“Previously the amount of genetics taught was limited and so we have gone right back to the beginning of their medical school training and reviewed what is being taught. We are not training them to be doctors in 2022, we’re training them to be doctors in the future. We start with the basics, and we follow the golden thread through the second year, the third year and on to the clinical years. They come and visit my paediatric clinic and see what genetics is like in action. It is important that our training reflects their need for when they are working in 10 or 20 years into their practices.”

Education should not just stop after graduating and Professor Moosa is passionate about sharing her knowledge with colleagues wherever possible. For example, she regularly visits the cleft clinic to interact with her surgical colleagues and speech therapists. It allows her to share information and this in turn is having positive results as there is a greater understanding of which cases would benefit from a referral for genetic testing. The ability to empower her colleagues is important, and this includes the midwives and nurses who work out in the rural communities, and who are often familiar with many generations within their communities. By recognising patterns they can highlight patients who might be affected by a rare disease.

As well as sharing information and upskilling colleagues it is also vital to empower families and caregivers. They are the ones who will have to be present at each clinic and advocate on behalf of themselves or their relatives.

“In the clinics, we often see grandmothers, who are the stars in our population. The parents may be busy with work or other children and so the grandmother will often take on the responsibility. They are the ones fighting day in and day out for their grandchildren but there has been very little support available for them. By giving the grandmothers more knowledge, they can start those conversations in their community, that were once perhaps stigmatizing families. In one clinic there is a grandmother who used lockdown to create Tiktok videos about her grandchild’s condition. She is changing perceptions and it is wonderful to see. We need to support these people so they too are taken care of and their mental health does not suffer. One of our initiatives is to create the opportunity for more peer to peer support and it will provide so many supportive relationships.”

“I would love first of all, for every person with a suspected rare disease to get a diagnosis as soon as possible. That includes us getting things done in the newborn period. Once they have a diagnosis it is important that there is buy-in from everybody, whether it’s in the hospital, in the school, in the community, or in our social welfare. We need to ensure the infrastructure is in place to support people and their caregivers throughout their journey. There’s a lot to do. But you know everything starts with the small steps. No matter whether you’re born in Cape Town or born in Kinshasa, you should have the same opportunities as others.”

Speaking about her dreams and hopes for the future Professor Moosa says;

I really am the lucky one because I get to meet all of them and they get to meet me as me. Each of them gets to touch my life. And that’s just amazing for me.