scholarly journals Dutch Founder SDHB Exon 3 Deletion in Patients with Pheochromocytoma-Paraganglioma in South Africa

2021 ◽  
Author(s):  
Debra M Gordon ◽  
Pablo Beckers ◽  
Emily Castermans ◽  
Sebastian Jcmm Neggers ◽  
Liliya Rostomyan ◽  
...  
Keyword(s):  
South Africa ◽  
Local Level ◽  
Founder Effects ◽  
Founder Mutations ◽  
Risk Genes ◽  
Endocrine Neoplasia ◽  
Single Center Study ◽  
Targeted Screening

Objective: Screening studies have established genetic risk profiles for diseases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma-paraganglioma (PPGL). Founder effects play an important role in regional/national epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in South Africa have not been explored in PPGL. Design: We performed a single-center study in South Africa of the germline genetic causes of isolated/syndromic neuroendocrine tumors. Methods: Next-generation panel and multiplex ligand-dependent probe amplification for endocrine neoplasia risk genes. Results: From a group of 13 patients we identified six with PPGL, four with sporadic or familial isolated pituitary adenomas (FIPA), and three with clinical MEN1; genetic variants were identified in 9/13 cases. We identified the Dutch founder exon 3 deletion in SDHB in two apparently-unrelated individuals with distinct ethnic backgrounds that had metastatic PPGL. Asymptomatic carriers with this Dutch founder SDHB exon 3 deletion were also identified. Other PPGL patients had variants in SDHB, SDHD and three MEN1 variants were identified among MEN1 and young-onset pituitary adenoma patients. Conclusions: This is the first identification of a Dutch founder effect for PPGL in South Africa. Awareness of the presence of this exon 3 SDHB deletion could promote targeted screening at a local level. Insights into PPGL genetics in South Africa could be achieved by studying existing patient databases for Dutch founder mutations in SDHx genes.

Role of 68Ga-DOTATATE PET/CT in patients with multiple endocrine neoplasia type 1 (MEN1)

Endocrine ◽  
2015 ◽  
Vol 52 (3) ◽  
pp. 488-494 ◽  
Author(s):  
Secondo Lastoria ◽  
Francesca Marciello ◽  
Antongiulio Faggiano ◽  
Luigi Aloj ◽  
Corradina Caracò ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Pet Ct

scholarly journals Industrial strategy and local economic development: The case of the foundry industry in Ekurhuleni Metro

2014 ◽  
Vol 8 (4) ◽  
pp. 448-464 ◽  
Author(s):  
T Phele ◽  
S Roberts ◽  
I Steuart
Keyword(s):  
South Africa ◽  
Economic Development ◽  
Local Economic Development ◽  
Local Level ◽  
Action Plans ◽  
Foundry Industry ◽  
The Past ◽  
Concrete Action

This  article explores the challenges for the development of manufacturing through a case study of the foundry industry in Ekurhuleni Metropolitan Municipality. Ekurhuleni Metro covers the largest concentration in South Africa, but the industry’s performance has been poor over the past decade.  The findings reported here highlight the need to understand firm decisions around investment, technology and skills, and the role of local economic linkages in this regard.  The differing performance of foundries strongly supports the need to develop concrete action plans and effective institutions at local level to support the development of local agglomerations.

Local Government Reforms in Federal Brazil, India and South Africa: A Comparative Overview

2013 ◽  
Vol 11 (3) ◽  
pp. 453-470
Author(s):  
Helder Do Vale
Keyword(s):  
South Africa ◽  
Local Government ◽  
Local Governments ◽  
Local Level ◽  
Transition To Democracy ◽  
Institutional Processes ◽  
The Past ◽  
Decision Making Processes ◽  
Government Reforms

This article examines the changes at the local level of government that have been taking place in Brazil, India and South Africa for the past thirty years as a result of complex federal decision-making processes. I summarize the most important federal traits of these countries and identify the role of key institutions behind the fiscal, political and administrative changes in local governments. The article draws on the institutional processes to dissect the anatomy of local government reforms in these countries and concludes that although the changes in local government structures and powers have been taken against the background of transition to democracy and/or democratic deepening, the scope of change in local government varied.

Suppression of 11β-hydroxysteroid dehydrogenase type 1 with RNA interference substantially attenuates 3T3-L1 adipogenesis

2008 ◽  
Vol 32 (3) ◽  
pp. 343-351 ◽  
Author(s):  
Yong Liu ◽  
Frank Park ◽  
Jennifer L. Pietrusz ◽  
Guangfu Jia ◽  
Ravinder J. Singh ◽  
...  
Keyword(s):  
Functional Role ◽  
Glucocorticoid Receptors ◽  
Local Level ◽  
Hydroxysteroid Dehydrogenase ◽  
Marker Genes ◽  
Nucleotide Substitutions ◽  
Hairpin Rna ◽  
Induction Of Differentiation

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regulates the local level of glucocorticoids, has been suggested to be involved in the development of obesity. A definitive functional role for 11β-HSD1 in adipogenesis, however, remains to be established. We developed 3T3-L1 cell lines stably transfected with a small hairpin RNA (shRNA) targeting 11β-HSD1. A shRNA containing two nucleotide substitutions was used as a control. Silencing of 11β-HSD1 substantially attenuated the accumulation of lipid droplets and the expression of adipogenesis marker genes, which was induced by a mixture containing either corticosterone or dexamethasone. Silencing of 11β-HSD1 increased the concentration of 11-dehydrocorticosterone in the culture supernatant but did not significantly affect the levels of corticosterone or dexamethasone. Translocation of glucocorticoid receptors to the nucleus in response to glucocorticoids was significantly attenuated by silencing 11β-HSD1. The number of cells entering the S phase of the cell cycle following the induction of adipogenesis was significantly reduced by silencing 11β-HSD1. 11β-HSD1 shRNA delivered by lentiviral vectors after the induction of differentiation, however, did not affect the progression of adipogenesis. These results indicate that 11β-HSD1 plays a significant functional role in the initiation of 3T3-L1 adipogenesis and provide new mechanistic insights into the role of 11β-HSD1 in the development of obesity and related diseases.

scholarly journals Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype–phenotype correlation

2007 ◽  
Vol 157 (3) ◽  
pp. 285-294 ◽  
Author(s):  
O Vierimaa ◽  
T M L Ebeling ◽  
S Kytölä ◽  
R Bloigu ◽  
E Eloranta ◽  
...  
Keyword(s):  
Clinical Features ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Missense Mutations ◽  
Founder Mutations ◽  
Phenotype Correlation ◽  
Endocrine Neoplasia ◽  
Mutation Carriers ◽  
Endocrine Neoplasia Type

Objective: The existence of genotype–phenotype correlation in multiple endocrine neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene in Northern Finland gave us an opportunity to compare clinical features among heterozygotes of different mutations. Design and methods: Study cohort included 82 MEN1 heterozygotes who were tested for MEN1 during the years 1982–2001. Medical records were reviewed for manifestations of MEN1, other tumours and cause of death by the end of August 2003. Logistic regression analysis was used in evaluating the impact of age, gender and mutational status of affected heterozygotes on the likelihood of developing manifestations of MEN1. Results: Founder mutations 1466del12 and 1657insC were found in 39 and 29 individuals, and D418N, G156R and R527X mutations in 9, 3 and 2 individuals respectively. Except for pituitary adenoma and nonfunctional pancreatic tumour (NFPT), age was a risk factor for all the disease manifestations. For NFPT, frameshift/nonsense mutations (1657insC, R527X) gave an odds ratio (OR) of 3.26 (95% confidence intervals (CI), 1.27–8.33; P = 0.014) compared with in-frame/missense mutations (1466del12, D418N, G156R); including the founder mutation carriers (n = 68) only, the 1657insC mutation gave an OR of 3.56 (CI, 1.29–9.83; P = 0.015). For gastrinoma, in-frame/missense mutations predicted the risk with an OR of 6.77 (CI, 1.31–35.0; P = 0.022), and in the founder mutations group the 1466del12 mutation gave an OR of 15.09 (CI, 1.73–131.9, P = 0.014). Conclusions: In this study population, NFPT was more common in the frameshift/nonsense or 1657insC mutation carriers, whereas gastrinoma was more common in the in-frame/missense or 1466del12 mutation carriers.

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