Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations.

The challenge of providing effective and integrated liver transplant services across South Africa's two socioeconomically disparate healthcare sectors has been faced by Wits Donald Gordon Medical Centre (WDGMC) since 2004. WDGMC is a private academic hospital in Johannesburg and serves to supplement the specialist and subspecialist medical training provided by the University of the Witwatersrand. Over the past 14 years, our liver transplant programme has evolved from a sometimes fractured service into the largest-volume liver centre in sub-Saharan Africa. The growth of our programme has been the result of a number of innovative strategies tailored to the unique nature of transplant service provision. These include an employment model for doctors, a robust training and research programme, and a collaboration with the Gauteng Department of Health (GDoH) that allows us to provide liver transplantation to state sector patients and promotes equality. We have also encountered numerous challenges, and these continue, especially in our endeavour to make access to liver transplantation equitable but also an economically viable option for our hospital. In this article, we detail the liver transplant model at WDGMC, fully outlining the successes, challenges and innovations that have arisen through considering the provision of transplant services from a different perspective. We focus particularly on the collaboration with the GDoH, which is unique and may serve as a valuable source of information for others wishing to establish similar partnerships, especially as National Health Insurance comes into effect.

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