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Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.

Background: Women who carry germline mutations in the breast-ovarian cancer susceptibility genes, BRCA1 and BRCA2, are at very high risk of developing breast and/or ovarian cancer. Both genes are tumour suppressor genes that protect all cells from deregulation, and there are reports of their involvement in other cancers that vary and seem to depend on the population investigated. It is therefore important to investigate the other associated cancers in different populations to assist with risk assessments., Objectives: To assess the cancer risk profile in BRCA-mutation-positive and negative South African breast-ovarian cancer families, mainly of Caucasian origin., Design: Descriptive study in which the prevalence of all cancers in the pedigrees of BRCA1- and BRCA2-mutation-positive groups and a group of families without mutations in either gene were compared with the general population., Results: As expected, female breast and ovarian cancer was significantly increased in all three groups. Furthermore, male breast cancer was significantly elevated in the BRCA2-positive and BRCA-negative groups. Stomach cancer prevalence was significantly elevated in the BRCA2-positive families compared with the general population., Conclusions: These results can be applied in estimation of cancer risks and may contribute to more comprehensive counselling of mutation-positive Caucasian breast and/or ovarian cancer families.

Objectives: To evaluate the willingness of medical doctors working at a tertiary hospital to participate in HIV vaccine trials, their perceptions of patients' willingness to participate, and the major reasons underlying these views., Design: A self-administered, anonymous postal survey conducted in two rounds between May and July 2001., Setting: A tertiary care hospital in the Western Cape., Subjects: All medical doctors listed on the hospital's staff directory., Outcome Measures: Willingness to participate in, and to recruit patients into, HIV vaccine trials, and the reasons for this., Results and Conclusions: Of the 289 individuals surveyed, 80% stated either that they would not be willing to participate in HIV vaccine trials or that they were unsure about their participation. Meanwhile, 37% stated that they would be willing to recruit patients into vaccine trials. The most common concerns with trial participation were the possibility of vaccine-induced infection and the possibility of testing positive for antibodies to HIV. The surprisingly low level of willingness to participate in trials in this sample of medical professionals highlights the importance of preparatory work to overcome substantial barriers to HIV vaccine trial participation.

Study Objective: To assess clinically South African patients with the putative diagnosis of Prader-Willi syndrome (PWS) and confirm this diagnosis by DNA/molecular analysis., Design: Prospective, nationally based, combined clinical and laboratory study., Main Results: Thirty-seven patients with a putative diagnosis of PWS were examined by clinical geneticists. Only 13 (35.1%) of these patients had the diagnosis of PWS confirmed by molecular analysis, and all 13 PWS patients had positive scores using the PWS consensus diagnostic criteria of Holm et al. The clinical features of the remaining 24 (64.9%) non-PWS patients were analysed and 23 did not have the neonatal, infantile and childhood features necessary to warrant consideration of a diagnosis of PWS; neither did they obtain a positive score according to Holm et al.'s criteria., Conclusion: PWS was confirmed in only 35% of South African patients with a putative PWS diagnosis, confirming that this condition is overdiagnosed and that the clinical diagnosis is difficult. Clinically, the diagnostic criteria of Holm et al. are of great assistance in making the diagnosis, but it remains essential to confirm the diagnosis by molecular analysis.

Intra-oral carcinoma is the third most common malignancy among men in developing countries, and carries a high mortality rate, particularly in Africa, where patients often present initially with lesions at an advanced stage. The present study was undertaken to determine the prevalence of human papillomavirus (HPV) DNA in oral squamous carcinoma in the west of the Northern Transvaal, an area where a large number of new cases has been diagnosed over the past few years. Paraffin blocks from 66 cases (51 men, 15 women; mean age 58.7 years) of oral squamous carcinoma were randomly selected. Blocks contained samples of both tumour and adjacent normal epithelium. The presence of HPV antigen was established by means of immunocytochemistry and HPV DNA by in situ hybridisation with radiolabelled probes for HPV-6, 11, 16 and 18. Immunocytochemistry for viral antigen was negative in all the specimens. HPV-18 was detected in normal epithelium adjacent to the tumour in one case only. It appears from our study that HPV is of limited importance in oral squamous cell carcinogenesis in the population studied.

A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immunocytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal carcinomas. Viral antigens could not be detected with immunocytochemistry in any of the specimens. HPV 6, 11 and 16 were detected in 3 oesophageal specimens. In one of these, HPV 16 was detected in normal as well as malignant cells. HPV 7 was detected for the first time in a laryngeal carcinoma. Our results confirm previous reports of possible HPV involvement in the pathogenesis of aerodigestive carcinomas.