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Background: Neural tube defects (NTDs) are anomalies of the central nervous system caused by the defective closure of the neural tube during early embryogenesis. A significant decline in the incidence of NTDs after folic acid fortification of food in South Africa was previously shown. Recently, clinical geneticists have voiced concerns that there is a possible resurgence in the number of NTDs. Objectives: The aim of this study was to determine the incidence of NTDs at a South African Hospital from 2012 to 2016. Methods: This is a retrospective cross-sectional study where all babies with NTDs born in, or referred to Universitas Hospital were included as study participants. Information was collected for both the mother and the baby from hospital records and data forms. Results: Seventy-seven cases of NTDs were captured from 2012 to 2016. The incidence of NTDs was 0.34/1000 births in the Free State province, and 1.21/1000 births if only the data for babies born in Universitas Hospital and Pelonomi Hospital were used. Further analysis showed a male: female ratio of 1:1. Open spina bifida was the most common defect at 71.4%. Conclusion: The incidence of NTDs in the Free State province was low compared to other South African and international studies. The incidence for the metropolitan hospitals is comparable to that of previous studies. This discrepancy is a marker of poor data recording and will impact healthcare planning. A statistically significant increase in NTDs could not be proven.

Background. A relatively high frequency of autosomal recessively inherited osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black southern African population. Affected persons may be severely handicapped as a result of frequent fractures, progressive deformity of the tubular bones and spinal malalignment. Objective. To delineate the molecular basis for the condition. Methods. Molecular investigations were performed on 91 affected persons from seven diverse ethnolinguistic groups in this population. Results. Following polymerase chain reaction amplification and direct cycle sequencing, FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected individuals in the study cohort. Haplotype analysis suggests that this mutation is identical among these OI-3-affected persons by descent, thereby confirming that they had a common ancestor. Compound heterozygosity of this founder mutation was observed, in combination with three different deleterious FKBP10 mutations, in six additional persons in the cohort. Four of these individuals had the c.831delC mutation. Conclusion. The burden of the disorder, both in frequency and severity, warrants the establishment of a dedicated service for molecular diagnostic confirmation and genetic management of persons and families with OI in southern Africa.

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.

Background. Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively. Objectives. To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin. Methods. A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic. Results. Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment. Conclusions. Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.

Background. Bardet Biedl syndrome (BBS) is a multisystem disorder characterised by obesity, polydactyly, intellectual disability and loss of vision due to a progressive retinopathy. Although typically a highly heterogeneous autosomal recessive disease, homozygosity for single mutation in BBS 10 has been identified in a significant number of affected individuals tested in South Africa (SA). Objectives. To delineate the ethnic distribution and clinical phenotype in a cohort of SA BBS patients with the K243IfsX15 mutation in BBS 10 and discuss the implications for genetic testing of and counselling for this disorder in SA. Method. This was a descriptive cross-sectional study collating clinical and laboratory data retrospectively in a genetically homogenous subgroup of BBS patients from SA. Results. A total of 76 patients from 74 families were tested. Homozygosity for the K243IfsX15 BBS 10 mutation was found in 50 families (67%) and heterozygosity for the same mutation in an additional two affected individuals. With the exception of one patient of mixed ancestry, all were black South Africans from different language groups. This is in keeping with the observation that BBS is more common in this ethnic group compared with white and coloured patients in SA, first made by Prof. Beighton nearly 3 decades ago. A subset of 15 patients available for detailed phenotyping confirmed consistency with well-described features of the disorder, with some overlap with other ciliopathies. The onset of visual impairment was early in our cohort, before the age of 8 years, cognitive impairment was significant, and renal and cardiac abnormalities were infrequently encountered. Conclusion. The high frequency of homozygosity for a single mutation in an ethnic subset of the SA population is strongly suggestive of a founder effect. This has allowed establishment of a diagnostic test with a high yield in our local population. Better understanding of the phenotype will improve earlier recognition of the disorder to allow for appropriate intervention. Testing can confirm but not negate a clinical diagnosis, and can permit carrier and prenatal testing in informative families.

Background. Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop­ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care. Objective. To assess the subjective attitude of patients towards pamidronate treatment. Methods. Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone. Results. Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons. Conclusion. This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.

This editorial examines a number of vitally important ethical, legal and scientific concerns that have to be addressed to ensure proper and ethical implementation of direct-to-consumer whole-exome sequencing in South Africa. Individuals taking part in this endeavour must be fully informed of the positive and negative sequelae.

Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. The severity of the disease is determined by age of onset, organ involvement including the degree of severity of muscle involvement, as well as rate of progression. PD is classified into two groups: infantile and late-onset, each having two subgroups. The need for two tests performed by separate methods (screening and confirmatory) is outlined. It is imperative to try to reduce the time to diagnosis and to recognise the possibilities of false-positive results. A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa.

Background: The doctor–patient relationship is important in determining the quality of healthcare provided. This study aimed to identify patient preferences regarding dress code, conduct and resources used by doctors during consultations in the public healthcare sector, Bloemfontein. Information from this study can be of benefit in determining policies and dress codes within hospitals and medical schools.Methods: This was a descriptive, cross-sectional study. Self-administered anonymous questionnaires were distributed at Bloemfontein’s National District Hospital to patients 18 years and older, waiting in the pharmacy and consultation queues.Results: Of the 500 questionnaires distributed 410 were analysed. Patients preferred doctors to wear formal attire. For female doctors this included a neat blouse (77.9%), smart pants (62.5%) or straight-cut jeans (51.4%) and flat pumps (56.3%). Patients preferred male doctors to wear collared shirts (52.4% and 57.6% for long- and short-sleeved shirts, respectively) with smart pants (66.8%) or straight-cut jeans (45.9%), and smart shoes (70.3%). Patients did not condone eating and drinking by doctors during consultations; work-related calls were deemed acceptable. The use of technological resources was not preferred.Conclusion: Patients in the public healthcare sector prefer a formal, professional consulting environment that is determined largely by the doctor’s attire and conduct during the consultation.

Introduction Microdeletions of chromosome 22 are common and have a prevalence of at least 1/4 000. Cardiac abnormalities, abnormal facial features and palatal abnormalities are frequently present in these patients. Aim To describe the cardiac lesions and selected measurable facial features in children from the Free State and Northern Cape presenting at the Cardiology Unit of the Universitas Academic Hospital complex in Bloemfontein. Methods This was a prospective study in which patients with abnormal facial characteristics were tested using a fluorescence in situ hybridisation (FISH) probe for the 22q11.2 microdeletion. Forty children tested positive for the microdeletion. All patients underwent an echocardiogram and where possible, facial anthropometric measurements were performed. Results The median age at diagnosis was 3.6 years (range 0.04 years, i.e. 2 weeks to 16.2 years). Tetralogy with or without pulmonary atresia was diagnosed in 43% (n = 17) of the children and truncus arteriosus in 20% (n = 8). A rightsided aortic arch was present in 43% (n = 17) of the patients. Mid-facial height was slightly longer (median z = 1.0; range –0.5 to 3.3) and width narrower (median z = –1.4; range –2.2 to 0.1) than normal. Ear height and width were notably small compared to normal, with median z-scores = –3.3 (range –4.8 to –2.6) and z = –2.4 (range –3.4 to –1.4), respectively. Conclusions Microdeletions of chromosome 22q11 are present in children from the Free State and Northern Cape. Conotruncal cyanotic heart lesions, especially tetralogy with or without pulmonary atresia and truncus arteriosus were the most frequent congenital cardiac diagnoses. A right-sided aortic arch was also commonly present in these children. Facial features varied and small ears were the most noteworthy anthropometric feature. A right-sided aortic arch with or without a congenital cardiac lesion, a long, narrow mid-face and small ears should alert the physician to the possibility of a microdeletion on the long arm of chromosome 22.

In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention.Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South Africa. NTDs as well as other birth defect rates were reported before and after fortification. Mortality data were also collected from two independent sources.This study shows a significant decline in the prevalence of NTDs following folic acid fortification in South Africa. A decline of 30.5% was observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49-0.98; p = .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally, oro-facial clefts showed no significant decline (5.7%). An independent perinatal mortality surveillance system also shows a significant decline (65.9%) in NTD perinatal deaths, and in NTD infant mortality (38.8%).The decrease in NTD rates postfortification is consistent with decreases observed in other countries that have fortified their food supplies. This is the first time this has been observed in a predominantly African population. The economic benefit flowing from the prevention of NTDs greatly exceeds the costs of implementing folic acid fortification.

Twenty-six highly polymorphic markers were used to determine the origin of the extra haploid chromosome set in 6 triploid fetuses of type II phenotype. All had reached the third trimester of pregnancy. The extra set was maternal in origin in all cases, supporting previous research indicating longer in utero survival of maternally-derived triploid fetuses. These findings provide evidence for an instance of genomic imprinting in humans.

The SBUV/TOMS measures the atmospheric ozone vertical profile and the solar ultraviolet spectrum, and provides a total ozone map by means of a mechanical scan across the Nimbus track. While the SBUV/TOMS instrument has noteworthy design features such as a state-of-the-art double monochromator and fixed optical components on a nonmetallic structure, its most significant characteristic is an optimum system design based on technology proven on the BUV instrument.

Comprehensive test specifications have been developed for the Beckman DK spectrophotometers, which may be applied, with appropriate modifications, to other recording photoelectric spectrophotometers.Average performance of a random sample of DK-2’s as defined by these tests, has been calculated.