Scientists find genetic mutation responsible for rare skin disease in Afrikaners
- Wits Communications
Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or ‘Oudtshoorn skin’, in Afrikaners.
KWE causes a redness of the palms and soles with consecutive cycles of peeling of large sections of thick skin, often exacerbated during winter months. Oudtshoorn is a town in theWestern Capeprovince ofSouth Africa where the disorder was present in large families.
Afrikaners are Afrikaans-language speakers descended from predominantly Dutch, German and French settlers, who arrived in South Africa in the 17th and 18th centuries. Afrikaners have a high risk for several genetic disorders, the best known being familial hypercholesterolaemia (inherited high cholesterol leading to heart attacks early in life) and porphyria (sensitivity of the skin to ultra-violet exposure and adverse reactions to specific drugs).
These disorders are common because of founder mutations brought to South Africa by small groups of immigrants who settled in the Cape of Good Hope and whose descendants are now spread throughout the country. KWE is one of these less well-known founder genetic disorders.
KWE was first described as a unique and discrete skin disorder in 1977 by Wits dermatologist, Professor George Findlay. He noticed that it occurred in families and had a dominant mode of inheritance – i.e., on average, if a parent has the condition about half the children inherit it in every generation.
In addition to identifying the genetic mutation for scientific purposes, this research now enables dermatologists to make a definitive diagnosis of KWE in patients. It further enables researchers to understand similar skin disorders and is a starting point for developing possible treatments.
Gene mutations
Since the late 1980s, three MSc and three PhD students at Wits researched the disorder, firstly under the supervision of Professor Trefor Jenkins and from about 1990 guided by Professor Michèle Ramsay, Director and Research Chair in the Sydney Brenner Institute for Molecular Bioscience.
In 1997, Wits MSc student Michelle Starfield and a group in Germany mapped the KWE trait to a region on the short arm of chromosome 8. The researchers showed that it was likely that the South African families all had the same mutation but that the German family had a different mutation. This research preceded the sequencing of the human genome and subsequent research focused on characterising this region of the genome and examining good candidate genes. The KWE mutation remained elusive.
In 2012 Thandiswa Ngcungcu, then a Wits MSc student in Human Genetics whom Ramsay supervised, chose KWE as a topic for her PhD. Ngcungu's research involved large-scale DNA sequencing during an internship on the Next Generation Scientist Programme in Novartis, Basel. The mutation was not detected by conventional data analysis so copy number variants (genetic changes) – where regions of the genome are duplicated or deleted – were investigated. Ngcungcu and the researchers then discovered a mutation in a region between genes that was present in all South African KWE-affected individuals studied.
During this time Dr Torunn Fiskerstrand, University of Bergen, Norway, independently discovered the genetic cause of KWE in Norwegians. Ramsay and Fiskerstrand collaborated. The different DNA duplications in the South African and Norwegian families overlapped at a critical genomic region called an enhancer (which ‘switches on’ the gene) – providing strong evidence that this was, in fact, the KWE mutation.
For over a year the scientists researched how this duplicated enhancer caused KWE. They demonstrated that the mutation causes a nearby gene to produce more protein than normal and that this abnormal expression was the likely cause of the skin peeling. Exactly twenty years after determining that the KWE mutation lies on chromosome 8, the mutation that causes KWE was identified and published.
Solving the mystery of KWE was a journey of data analysis, ancestry mapping, genomic comparison and global collaboration. Ngcungcu continues her work as a postdoctoral fellow examining the genetics of another skin disorder, albinism, and as a lecturer in the Division of Human Genetics at Wits from July 2017.
SA kids not on the ball
- Wits Communications
Wits researchers and their peers have awarded South African children a C-grade on the Healthy Active Kids South Africa Report Card for physical activity levels.
Dr Rebecca Meiring, lead researcher in exercise physiology at the Movement Physiology Research Laboratory in the School of Physiology at Wits, says: “Researchers from institutions across South Africa got together to research overall physical activity in children in South Africa. Unfortunately, kids in South Africa scored a C in the Healthy Active Kids South Africa Report Card, meaning that only about half of children in South Africa get enough exercise.”
The paper, “Results from South Africa’s 2016 Report Card on Physical Activity for Children and Youth” was published in the Human Kinetics Journals.
Wits researchers and their peers have awarded South African children a C-grade on the Healthy Active Kids South Africa Report Card for physical activity levels.
Globally fewer than 20 percent of children and youth meet recommendations for physical activity. For the first time in history there are now more children who are overweight and obese compared with those who are under-nourished or stunted.
The South African Medical Research Council indicates that 40% of adult deaths in SA result from chronic lifestyle diseases with direct links to lack of regular aerobic exercise. However, less is known about the physical activity of children.
“There is still a lot that is unknown about the activity level of children across all backgrounds, so the best way to inform policy-makers is to fill these knowledge gaps by conducting research in these areas. This is how policy-makers can be better informed to make changes at grassroots level. We really need special efforts – not just from researchers in the area of physical activity, but also from teachers, parents, coaches, all the way to policy-makers – to try and improve lifestyles and health in South Africa,” says Meiring.
Dr Estelle Watson, a biokinetics researcher at the Centre, says: “The research also indicates less-than-optimal intervention programmes. Less than half of SA children and youth take part in organised sporting activities. Even more concerning is the fact that there is a lower participation rate in girls.”
The Healthy Active Kids South Africa Report Card
The Healthy Active Kids South Africa Report Card (HAKSA) 2016 reflects the best available scientific evidence from the last five years concerning physical activity and healthy eating in South African children and youth. It builds on the evidence base gathered for the previous report cards in 2007, 2010, and 2014. The report looks beyond whether or not South Africa’s children and youth are meeting recommendations, and attempts to unpack factors that contribute to making healthy choices easier, or those that stand in the way.
HAKSA 2016 physical activity indicators
From evidence presented in the 2014 report card physical activity appeared to improve overall. Girls, however, tend to take part in less physical activity compared with boys.
Physical fitness and motor proficiency, organised sport participation, and the role of school sport are areas that have not improved or declined since the last report, suggesting that engagement in these areas is not being promoted effectively.
Sedentary behaviour (time spent sitting or lying) among South African children and youth is high (more than 2 hours of screen time per day) and no studies have indicated an improvement since 2014. The area of sedentary behaviour is understudied in South African populations.
Peer and family support for physical activity participation and the role of the community and the built environment remain areas which lack the drive to promote physical activity. There is a need for community-based strategies, including maintaining existing physical activity infrastructure to enable children to increase physical activity levels.
Government engagement and investment in children’s physical activity remains a focus for the Department of Basic Education although compliance to government programmes remains poor. There is a disconnect between the promotion and the uptake of physical activity programmes.
HAKSA 2016 nutrition indicators
Overweight and obesity in children and adolescents in South Africa is high. The prevalence of obesity is in the region of 15 – 30% (boys and girls and children and adolescents combined). The levels are similar to those seen in American children.
The undernutrition rate is slowly declining. However, it remains high in boys and in children from low socioeconomic backgrounds.
There is limited evidence available about fruit and vegetable intake, snacking behaviours (including sugar intakes) and fast food intake. However, the limited studies available suggest that South African children perform poorly in these areas.
There is also limited evidence that programmes/avenues available to support healthy eating are actually improving children and adolescent nutrition. These programmes include the National School Nutrition Programme, school vegetable gardens, school tuck shops, and the role of advertising and media.
A problem with healthy eating, it seems, is that there is still a certain percentage of the population with inadequate access to food, juxtaposed with the high prevalence of obesity in children. This area warrants further research.
The 2016 report concludes that, unfortunately, not much has changed since the 2014 report. Although there are promising initiatives being implemented in the private and public sectors uptake of these initiatives remains low. Only if engagement occurs at all levels can we begin to increase physical activity and support healthy eating in South African children.
More about the Wits Movement Physiology Research Laboratory (MPRL)
The MPRL consists of a vibrant and dynamic research team. We believe that exercise and physical activity play an essential role in treating, and even preventing, chronic diseases of lifestyle such as obesity, hypertension, diabetes, heart disease and osteoporosis. We are also interested in gaining knowledge about the diseases which limit exercise and movement. As such, our research focuses on exercise and physical activity as a lifestyle tool to improve the health of South Africans, both young and old.
The MPRL consists of the Exercise Physiology Lab and the Biomechanics Lab. The key research areas are:
Physical Activity and Health
Sports Performance
Neuro-cognitive Motor Physiology.
There are currently 3 permanent full-time staff members in the lab undertaking each of the three research areas.
Betrayal of the promise: How South Africa is being stolen
- Wits Communications
Wits researchers co-authored a state capture report produced by the State Capacity Research Project, an interdisciplinary, interuniversity research partnership.
The Public Affairs Research Institute (PARI), associated with Wits University, is among these partners.
Wits alumnus, Professor Ivor Chipkin is Executive Director of PARI, which he founded in 2010. Chipkin is a Visiting Professor in the School of Social Sciences at Wits and a former researcher at the Wits Institute for Social and Economic Research (WiSER).
Dr Mbongiseni Buthelezi is Research Manager at PARI and a Research Associate in the School of Social Sciences at Wits.
Professor Adam Habib, Vice-Chancellor and Principal of Wits, who attended the launch said the report is "a must-read for all interested in the future of SA".
Wits Research Director amongst southern Africa’s best
- Wits Communications
Dr Robin Drennan, Director of Research Development at Wits, has been awarded by his southern African peers for his contribution to research management.
The Southern African Research and Innovation Management Association (SARIMA) gave Drennan the Distinguished Contribution to Research Management Profession Award at the SARIMA 2017 Annual Conference held in Windhoek, Namibia from 22-25 May 2017.
“It is a privilege to work as a research manager at Wits and to contribute to the development of the profession in South Africa. My work involves stewarding research, which often means spending time talking with a range of wonderful academic researchers who do the most amazing things. Their insight and drive to seek out the truth is inspirational and makes it an absolute pleasure to provide them with support and encouragement,” says Drennan.
The award includes a trophy and R30 000 to cover the costs of an international trip to a suitable research management conference.
“I will probably use the prize money to attend the International Network of Research Management Societies Conference [INORMS] in Edinburgh, Scotland from 4-7 June 2018,” says Drennan.
The SARIMA award acknowledges Drennan’s role in the profession of research management. He developed an information and technology communication (ITC) system at Wits for the collection, submission and verification of research publications. This new system enabled collection of 16 percent more publications than its predecessor, thus earning the University R160m.
Drennan is actively involved in the Consortium for the Advancement of Research Training in Africa (CARTA) and has facilitated a dozen international research management training workshops.
Drennan’s contribution to research development is evident in his management and mentorship of 22 members of Wits staff, his support of 50 research managers at Wits, and his mentorship of three peers in other research institutions. Drennan himself holds a PhD in Chemistry from Rhodes University.
“I dedicate this award to the almost 100 people at Wits who also carry out research and innovation management. It is these people and their often hidden contributions that help to grow the University’s research intensity,” he says.
