Cystic fibrosis genetic counselling: an audit of counsellees and their at-risk relatives

ABSTRACT Cystic fibrosis (CF) is an autosomal recessive disorder that occurs in all ethnic groups. Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene are responsible for pulmonary obstruction, chronic lung infections, pancreatic insufficiency, meconium ileus, failure to thrive and infertility. Genetic testing for CF at the DNA level is available. A diagnosis of CF in an individual has implications for other family members and so genetic counselling should form part of CF management. Genetic counselling has been offered by the Clinical Unit of the Division of Human Genetics, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, for many years. At the beginning of 2006, genetic services were introduced into the CF Clinics of Johannesburg Hospital by way of specialist Genetic Counselling Clinics. The study aimed to determine who utilises the CF genetic counselling services and why, to estimate the number of at-risk relatives per family, and how many of them had mutation testing and genetic counselling. Finally, the study explored what impact the specialist Genetic Counselling Clinics had on the overall service of genetic counselling. The files of 153 families seen for CF genetic counselling from 1990 to 2006 were analysed. The majority of counsellees (93%) were white. Most counsellees were parents of CF probands (35%). Relatives with carrier risks of 67% (siblings) and 50% formed only 7% and 6% of all counsellees respectively. Most individuals attended genetic counselling in order to gather information. On average, 5.9 ± 3.45 families were seen for CF genetic counselling per year from 1990 to 2005, whereas in 2006, 58 families were seen. Paediatrician, physician and nurse referrals increased notably during 2006 compared to prior years. In 140 unrelated CF-affected families, 1991 at-risk relatives, with carrier risks above 25%, were identified. Only 11% of these relatives had mutation testing and only 8% attended genetic counselling. Uptake of genetic counselling is greater when the service is integrated into CF treatment clinics than when it is offered externally. The low uptake of mutation testing and genetic counselling by at-risk relatives suggests that new methods of educating individuals for cascade screening and testing are required

Genetic susceptibility to fetal alcohol syndrome in the Northern Cape coloured population: Potential roles of astrotactin and reelin

Student Number : 0416521T - MSc(Med) dissertation - School of Pathology - Faculty of Health SciencesFetal alcohol spectrum disorder (FASD) encompasses a range of conditions induced by prenatal alcohol exposure. Fetal alcohol syndrome (FAS) is the most severe of these conditions. FAS is characterised by discriminating facial features along with growth deficiencies and central nervous system abnormalities. FASD is a growing concern in South Africa, particularly in the Northern and Western Cape Provinces. In the Northern Cape, astounding prevalence rates of 122 and 73.8 per 1000 school entry children have been established for the towns of De Aar and Upington respectively. Studies involving twin concordance research and animal models have indicated that there is a genetic influence contributing towards FAS susceptibility in individuals. FAS is considered a complex disease whereby both genetic and environmental factors interact in disease pathogenesis. For this reason a case-control study involving the investigation of appropriate candidate genes was conducted. The neuronal migration pathway in the developing brain is targeted by prenatal alcohol exposure. The astrotactin (ASTN) and reelin (RELN) genes were selected for investigation based on their fundamental role in neuronal migration. A FAS case-control study involving 45 cases and 112 controls was conducted on the Northern Cape Coloured population. Four single nucleotide polymorphisms (SNPs) including missense and non-coding variants were selected within ASTN and four missense SNPs were selected within RELN. The study aimed to determine the genotype and allele frequencies of the variants within the case and control groups and to assess whether any association between the gene variants and the predisposition to FAS existed. Statistical analyses indicated a significant genotypic association (P= 0.049) between RELN’s rs607755 marker; the C/T genotype was more likely to be found amongst controls thus inferring a possible protective effect against FAS. A logistic regression model supported the above association by indicating the C/T genotype as being independently significant (P= 0.026). The most limiting factor of this study was the small sample size and consequent lack of power to detect genes with minor effects. It would therefore be suggested that the study be repeated once a larger sample size has been established. A larger sample size would increase the chances of detecting true associations between genes of minor effect and FAS, thus minimising false-positive associations from arising

The Success Of Chains: Customer Loyalty Or Customer Comfort?

The quest to understand customer behaviour has led researchers down many interesting paths. Is it satisfaction with the product, a feeling of belonging, a basic need, or perhaps something more? The literature lends itself to many theories and constructs that try to pin point what makes the consumer tick. Generally the literature defines both physical and psychological aspects of the consumer, that can help better predict the behaviour of the market. The research leaves many questions: Does one rely on the other? Are we measuring too much? Or are we missing the main points? This paper will look at the psychological aspect of the literature in trying to develop the Consumer Comfort construct (Spake, Beatty, Brockman and Crutchfield 2003), and to identify the basic determinates needed to measure buyer behaviour

Gestational diabetes mellitus in Africa: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is any degree of impaired glucose tolerance first recognised during pregnancy. Most women with GDM revert to normal glucose metabolism after delivery of their babies; however, they are at risk of developing type 2 diabetes later in life as are their offspring. Determining a country's GDM prevalence can assist with policy guidelines regarding GDM screening and management, and can highlight areas requiring research. This systematic review assesses GDM prevalence in Africa. METHODS AND FINDINGS: Three electronic databases were searched without language restrictions; PubMed, Scopus and the Cochrane Library. Thirty-one search terms were searched. Eligible articles defined GDM, stated what GDM screening approaches were employed and reported GDM prevalence. The reporting quality and risk of bias within each study was assessed. The PRISMA guidelines for systematic reviews were followed. The literature search identified 466 unique records. Sixty full text articles were reviewed of which 14 were included in the systematic review. One abstract, for which the full text article could not be obtained, was also included. Information regarding GDM classification, screening methods and prevalence was obtained for six African countries; Ethiopia (n = 1), Morocco (n = 1), Mozambique (n = 1), Nigeria (n = 6), South Africa (n= 4) and Tanzania (n = 1). Prevalence figures ranged from 0% (Tanzania) to 13.9% (Nigeria) with some studies focussing on women with GDM risk factors. Most studies utilised the two hour 75 g oral glucose tolerance test and applied the World Health Organization's diagnostic criteria. CONCLUSIONS: Six countries, equating to 11% of the African continent, were represented in this systematic review. This indicates how little is known about GDM in Africa and highlights the need for further research. Considering the increasing public health burden of obesity and type 2 diabetes, it is essential that the extent of GDM is understood in Africa to allow for effective intervention programmes.This is the final published version of the article. It was originally published here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0097871

The Success Of Chains: Customer Loyalty Or Customer Comfort?

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Breast cancer in high-risk Afrikaner families: Is BRCA founder mutation testing sufficient?

Background. Germline pathogenic mutations in cancer susceptibility genes result in inherited cancer syndromes. In the Afrikaner population of South Africa (SA), three founder mutations in the BRCA genes that lead to hereditary breast and ovarian cancer syndrome (HBOCS) have been identified.Objectives. To investigate the uptake and type of molecular testing performed on patients for HBOCS, to determine the prevalence of the three Afrikaner founder BRCA mutations as well as non-founder BRCA mutations in the study population, and to analyse the utility of two mutation prediction models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and Manchester scoring method) in assisting with the decision for the most cost-effective testing option.Methods. A retrospective file review was performed on counsellees of self-reported Afrikaner ancestry from Johannesburg, SA (2001 - 2014), with a personal or family history of breast and/or ovarian cancer. Demographic and family history information was recorded and Manchester and BOADICEA scores were calculated for each patient.Results. Of 86 unrelated counsellees whose files were reviewed, 54 (62.8%) underwent BRCA genetic testing; 18 (33.3%) tested positive for a mutation, and 14 of these (77.8%) for an Afrikaner founder mutation. Twelve counsellees had the BRCA2 c.7934delG mutation. Four non-founder mutations were identified. BOADICEA scores were significantly higher in counsellees who tested positive for a mutation than in those who tested negative.Conclusions. Founder mutation testing should be performed as a first-line option. BOADICEA is very useful in identifying counsellees at high risk for a BRCA mutation and also assists with the decision to pursue further testing following a negative founder mutation result. These findings assist in guiding an informed genetic counselling service for at-risk individuals with an Afrikaner background

British Romanticism and the Global Climate

As a result of developments in the meteorological and geological sciences, the Romantic period saw the gradual emergence of attempts to understand the climate as a dynamic global system that could potentially be affected by human activity. This chapter examines textual responses to climate disruption cause by the Laki eruption of 1783 and the Tambora eruption of 1815. During the Laki haze, writers such as Horace Walpole, Gilbert White, and William Cowper found in Milton a powerful way of understanding the entanglements of culture and climate at a time of national and global crisis. Apocalyptic discourse continued to resonate during the Tambora crisis, as is evident in eyewitness accounts of the eruption, in the utopian predictions of John Barrow and Eleanor Anne Porden, and in the grim speculations of Byron’s ‘Darkness’. Romantic writing offers a powerful analogue for thinking about climate change in the Anthropocene

The prevalence of gestational diabetes mellitus amongst black South African women is a public health concern.

AIMS: This study aimed to determine the prevalence of gestational diabetes mellitus (GDM) amongst black South African women, describe GDM-associated risk factors and clinical management, and evaluate the efficacy of the fasting plasma glucose reading in diagnosing GDM. METHODS: A cross-sectional screening study was performed. Pregnant women were recruited from the Chris Hani Baragwanath Academic Hospital in Johannesburg. A total of 1906 women underwent a two-hour 75 g oral glucose tolerance test at 24-28 weeks gestation. The World Health Organization's 2013 criteria were used to diagnose GDM. RESULTS: A total of 174/1906 (9.1% (95% confidence interval (CI) 7.9, 10.5)) women were diagnosed with GDM. These women had significantly higher weights and body mass indexes (BMIs), were significantly older, of higher household socioeconomic status, more likely to report a family history of diabetes, and more likely to be diagnosed with anaemia than women without GDM. An age of ≥35 years, BMI ≥ 30 kg/m2, and a family history of diabetes were significant risk factors. The fasting plasma glucose reading had a high sensitivity (83.3% (95% CI 77.0, 88.5)) in diagnosing GDM and 56.9% of the women with GDM were managed by diet therapy alone. CONCLUSION: This is the largest GDM prevalence study in South Africa to date. A diagnosis of GDM increases the risk of both mother and child developing Type 2 diabetes which causes further health complications, decreases longevity, and burdens a country's healthcare system. Therefore, a GDM prevalence of 9.1% is concerning and warrants further discussion around current GDM screening policies

Prevalence of Gestational Diabetes Mellitus (GDM) in Africa.

<p>*Refer to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097871#pone-0097871-t001" target="_blank">Table 1</a>;</p><p>**Could not obtain full text article.</p