Risk assessment of variant Creutzfeldt-Jakob disease in corneal transplantation

Purpose: While corneal transplantation is known to have a potential risk of transmission of variant Creutzfeldt-Jacob Disease (vCJD), the magnitude of this risk has not been quantified. Observations: A case report is presented of a 73 year-old man with a penetrating keratoplasty graft from corneal tissue that was recalled after transplantation due to risk of vCJD because it was later discovered that the donor had traveled to the United Kingdom (UK). Probabilities of vCJD transmission were extrapolated using Creutzfeldt-Jacob Disease (CJD) mortality (incidence) rate, all-cause death rate, and rate of recovery for intended transplantation. Conclusions: An overestimate of the risk of transplanting a cornea infected with vCJD in 2018 was 1 in 940,000. The true risk of vCJD transmission would be even lower due to an incomplete infectivity rate. We conclude that the risk of transmission of latent vCJD by corneal transplantation from a donor who traveled to the UK from 1980 to 1996 is exceedingly low

The discovery of human genetic variations and their use as disease markers: Past, present and future

10.1038/jhg.2010.55Journal of Human Genetics557403-415JHGE

ATP-sensitive potassium channels in health and disease

The ATP-sensitive potassium (KATP) channel plays a crucial role in insulin secretion and thus glucose homeostasis. KATP channel activity in the pancreatic β-cell is finely balanced; increased activity prevents insulin secretion, whereas reduced activity stimulates insulin release. β-cell metabolism tightly regulates KATP channel gating, and if this coupling is perturbed, two distinct disease states can result. Diabetes occurs when the KATP channel fails to close in response to increased metabolism, whereas congenital hyperinsulinism results when KATP channels remain closed even at very low blood glucose levels. In general there is a good correlation between the magnitude of KATP current and disease severity. Mutations that cause a complete loss of KATP channels in the β-cell plasma membrane produce a severe form of congenital hyperinsulinism, whereas mutations that partially impair channel function produce a milder phenotype. Similarly mutations that greatly reduce the ATP sensitivity of the KATP channel lead to a severe form of neonatal diabetes with associated neurological complications, while mutations that cause smaller shifts in ATP sensitivity cause neonatal diabetes alone. This chapter reviews our current understanding of the pancreatic β-cell KATP channel and highlights recent structural, functional, and clinical advances