Epidemiology, pathophysiology and putative genetic basis of carbamazepine- and oxcarbazepine-induced hyponatremia.

The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ- and OXC-induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway.

Veterinary and human biobanking practices: enhancing molecular sample integrity.

Animal models have historically informed veterinary and human pathophysiology. Next-generation genomic sequencing and molecular analyses using analytes derived from tissue require integrative approaches to determine macroanalyte integrity as well as morphology for imaging algorithms that can extend translational applications. The field of biospecimen science and biobanking will play critical roles in tissue sample collection and processing to ensure the integrity of macromolecules, aid experimental design, and provide more accurate and reproducible downstream genomic data. Herein, we employ animal experiments to combine protein expression analysis by microscopy with RNA integrity number and quantitative measures of morphologic changes of autolysis. These analyses can be used to predict the effect of preanalytic variables and provide the basis for standardized methods in tissue sample collection and processing. We also discuss the application of digital imaging with quantitative RNA and tissue-based protein measurements to show that genomic methods augment traditional in vivo imaging to support biospecimen science. To make these observations, we have established a time course experiment of murine kidney tissues that predicts conventional measures of RNA integrity by RIN analysis and provides reliable and accurate measures of biospecimen integrity and fitness, in particular for time points less than 3 hours post-tissue resection.

Hyperactive behavior in a family with autosomal dominant lateral temporal lobe epilepsy caused by a mutation in the LGI1/epitempin gene.

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the leucine-rich glioma-inactivated 1 (LGI1) gene have been reported in up to 50% of families with ADLTE. Attention-deficit/hyperactivity disorder (ADHD) symptoms have not yet been reported in these families. Clinical data were collected from a family with five affected members. Leucine-rich glioma-inactivated 1 exons and boundaries were sequenced by standard methods. Attention-deficit/hyperactivity disorder symptoms were scored based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Affected members had seizures with auditory features and psychic auras, and some experienced nightmares. A heterozygous c.431+1G>A substitution in LGI1 was detected in all members. Significantly more hyperactivity symptoms were found in family members carrying the LGI1 mutation. This study expands the phenotypic spectrum associated with ADLTE due to LGI1 mutation and underlines the need for more systematic evaluation of ADHD and related symptoms.

A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.

Hereditary hemochromatosis (HH) is a very common disorder characterized by iron overload and multi-organ damage. Several genes involved in iron metabolism have been implicated in the pathology of HH (refs. 1-4). We report that a mutation in the gene encoding Solute Carrier family 11, member A3 (SLC11A3), also known as ferroportin, is associated with autosomal dominant hemochromatosis.

Review paper: Gene expression profiling in veterinary and human medicine: overview of applications and proposed quality control practices.

High throughput molecular analysis of veterinary tissue samples is being applied to a wide range of research questions aimed at improving survival, development of diagnostic assays, and improving the economics of commercial production of animal products. Many of these efforts also, implicitly or explicitly, have ramifications for the clinical care of humans and, potentially, animals. Here we provide an overview of applications of gene expression profiling in veterinary research and practice. We then focus on the current state of quality control and quality assurance efforts in gene expression profiling studies, underscoring lessons learned from such analysis of human samples. Finally, we propose practices aimed at ensuring the reliability and reproducibility of such assays. The implementation of quality assurance practices by a trained pathologist is an essential link in the chain of events leading ultimately to reliable and reproducible research findings and appropriate clinical care.