Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population

No Abstract

Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population

Objective. Familial hypercholesterolaemia (FH) is a common genetic disease characterised by strikingly elevated. plasma cholesterol concentration, which can lead to premature coronary death if left untreated. In this study DNA diagnosis of FH, which allows detection before onset of clinical symptoms, was evaluated against biochemical parameters routinely used to identify subjects with FH.Design. A population-based strategy was used to identify low-density lipoprotein receptor (LDLR) gene defects in South Africans with clinical signs of FH, followed by a family-based DNA screening approach for presymptomatic diagnosis of FH.Results. DNA screening of 790 at-risk relatives for the FHrelated mutations identified in 379 index cases, allowed accurate disease diagnosis in an additional 338 relatives and exclusion of the relevant mutation in 452 individuals. The sensitivity and speeifidty of the diagnosis, based on total cholesterol values measured in family members of FH heterozygous index cases with one of the three founderrelated mutations, D154N, D206E and V408M, were 89.3% and 81.9%, respectively.Conclusion. The predominance of 10 LDLR gene mutations in the local population justifies population-directed D A diagnosis of FH in South Africa on a routine basis, particularly since expression of the defective gene measured in biochemical tests does not allow accurate diagnosis of FH in all cases. D A testing provides a definitive tool for family tracing aimed at pre-clinical diagnosis and preventive treatment of FH

Facilitating technology-enhanced external examination moderation during the Covid-19 pandemic

Due to the Covid-19 pandemic and associated travel restrictions, the physical presence of international external examiners was a challenge when assessing the exit level outcomes of the MSc (Dent) in Paediatric Dentistry at the University of the Western Cape. External moderation of final examinations ensure an acceptable standard, coverage of content as specified by the programme outcomes and eliminates bias during assessment. Internationalization of the moderation andexamination process allows countries to compare and maintain international standards and graduate attributes expected for professional qualifications.Qualifications requiring assessment of skills often rely on ObjectiveStructured Clinical Examinations, Objective Structured Practical Examinations and simulated cases in combination with an oral examination, which requires the presence of all examiners to assess the student. This paper describes how the final examination in this MSc (Dent) degree was adapted and conducted in order to overcome the challenges of the Covid-19 pandemic, to maintain the academic integrity and rigour of the programme. A narrative essay-style approach was adopted, which reflects on the challenges and opportunities created by Covid-19. The adapted assessment method proved to be an effective alternative to the more traditional assessment approaches employed pre-Covid

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

The original publication is available at http://jmg.bmj.com/In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenicLDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.Harry and Doris Crossley FoundationSouth African Medical Research CouncilUniversity of StellenboschBritish Heart Foundation (grant no PG/96013)Publisher's versio

Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population

CITATION: Vergotine, J., Thiart, R. & Kotze, M. J. 2001. Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population. South African Medical Journal, 91(12):1053-1059.The original publication is available at http://www.samj.org.zaObjective. Familial hypercholesterolaemia (FH) is a common genetic disease characterised by strikingly elevated plasma cholesterol concentration, which can lead to premature coronary death if left untreated. In this study DNA diagnosis of FH, which allows detection before onset of clinical symptoms, was evaluated against biochemical parameters routinely used to identify subjects with FH. Design. A population-based strategy was used to identify low-density lipoprotein receptor (LDLR) gene defects in South Africans with clinical signs of FH, followed by a family-based DNA screening approach for presymptomatic diagnosis of FH. Results. DNA screening of 790 at-risk relatives for the FH-related mutations identified in 379 index cases, allowed accurate disease diagnosis in an additional 338 relatives and exclusion of the relevant mutation in 452 individuals. The sensitivity and specificity of the diagnosis, based on total cholesterol values measured in family members of FH heterozygous index cases with one of the three founder-related mutations, D154N, D206E and V408M, were 89.3% and 81.9%, respectively. Conclusion. The predominance of 10 LDLR gene mutations in the local populations justifies population-directed DNA diagnosis of FH in South Africa on a routine basis, particularly since expression of the defective gene measured in biochemical tests does not allow accurate diagnosis of FH in all cases. DNA testing provides a definitive tool for family tracing aimed at pre-clinical diagnosis and preventive treatment of FH.Publisher’s versio

A Giant Cell Fibroma and Focal Fibrous Hyperplasia in a Young Child: A Case Report

A case of two fibrotic lesions of the oral mucosa in a 17-month-old African-American female is reported. Both lesions occurred on the anterior maxilla, one lesion pedunculated on the buccal attached gingiva and the other lesion sessile on the palate. Histological examination characterized the buccal lesion as focal fibrous hyperplasia (FFH) and the palatal lesion as a giant cell fibroma (GCF). A case is made for continuing the consideration of GCF as a histologically distinct entity from FFH but that no difference in clinical impact between the two lesions exists

Die rol van geskiedenis as skoolvak in die bevordering van opvoeding vir vrede

Tesis (M. Ed.) -- Universiteit van Stellenbosch, 1997.Bibliografie.Een kopie mikrofiche.Full text to be digitised and attached to bibliographic record

Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the South African population.

GesondheidswetenskappeVerloskunde En GinekologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]