The ethics of conducting observational tobacco research without providing treatment to people who use tobacco
A case example from South Africa
Bibliographic Data
Introduction Replication of the nuclear genome is an essential step for cell division. Pathogenic variants in genes coding for highly conserved components of the DNA replication machinery cause Meier-Gorlin syndrome (MGORS). Objective Identification of novel genes associated with MGORS. Methods Exome sequencing was performed to investigate the genotype of an individual presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. The analysis of the candidate variants employed bioinformatic tools, in silico structural protein analysis and modelling in budding yeast. Results A novel homozygous missense variant NM_016095.2:c.341G>T, p.(Arg114Leu), in GINS2 was identified. Both non-consanguineous healthy parents carried this variant. Bioinformatic analysis supports its classification as pathogenic. Functional analyses using yeast showed that this variant increases sensitivity to nicotinamide, a compound that interferes with DNA replication processes. The phylogenetically highly conserved residue p.Arg114 localises at the docking site of CDC45 and MCM5 at GINS2. Moreover, the missense change possibly disrupts the effective interaction between the GINS complex and CDC45, which is necessary for the CMG helicase complex (Cdc45/MCM2–7/GINS) to accurately operate. Interestingly, our patient’s phenotype is strikingly similar to the phenotype of patients with CDC45 -related MGORS, particularly those with craniosynostosis, mild short stature and patellar hypoplasia. Conclusion GINS2 is a new disease-associated gene, expanding the genetic aetiology of MGORS
Environmental health · Observational study · Political science · Tobacco use · Global Cancer Incidence and Screening · Global Public Health Policies and Epidemiology · Health Systems, Economic Evaluations, Quality of Life · Medicine · Internal Medicine
What Makes Clinical Research in Developing Countries Ethical? The Benchmarks of Ethical Research
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St-Century Hazards of Smoking and Benefits of Cessation in the United States
Cohort Profile
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