Dysregulation of Circadian Rhythm Gene Expression in Cystic Fibrosis Mice.

Cystic fibrosis (CF) is autosomal recessive disease that affects multiple body systems. CF patients often experience sleep disturbances, altered sleep patterns, and sleep apnea. Sleep in mammals is controlled in part by circadian clock genes, including Clock, Bmal1, Period1, Period2, Cryptochrome1, and Cryptochrome2. The purpose of this study was to gain a better understanding of the biological underpinnings of disordered sleep experienced in CF. To accomplish this, we evaluated circadian clock gene expression profiles in CF and wildtype mice, divided into two subgroups each based on sleep condition. One subgroup of each genotype was permitted to maintain their sleep-wake cycle while the other was deprived of sleep for six hours prior to sacrifice. Brain, skeletal muscle, jejunum, colon, lung and adipose tissues were collected from each mouse. Quantitative polymerase chain reaction (PCR) was used to quantify expression of Clock, Bmal1, Period1, Period2, Cryptochrome1 and Cryptochrome2, and expression levels were compared between study groups. Our comparisons showed distinct differences between the CF groups and the wildtype groups under both sleep conditions. Additionally, we found the CF mice that had been sleep deprived had severely dysregulated expression of all measured genes in the lung apart from Cry1. Our findings suggest that (1) disordered sleep in CF may be caused by circadian system dysregulation and (2) the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) is a causative factor in the dysregulated circadian clock gene expression profiles of CF mice.

Reduction of Health Care Costs and Improved Appropriateness of Incoming Test Orders: the Impact of Genetic Counselor Review in an Academic Genetic Testing Laboratory.

The goal of this study was to evaluate the impact of genetic counselor (GC) review of incoming test orders received in an academic diagnostic molecular genetics laboratory. The GC team measured the proportion of orders that could be modified to improve efficiency or sensitivity, tracked provider uptake of GC proposed testing changes, and calculated the health care dollar savings resulting from GC intervention. During this 6-month study, the GC team reviewed 2367 incoming test orders. Of these, 109 orders (4.6%) were flagged for review for potentially inefficient or inappropriate test ordering. These flagged orders corresponded to a total of 51 cases (1-5 orders for each patient), representing 54 individuals and including 3 sibling pairs. The GC team proposed a modification for each flagged case and the ordering providers approved the proposed change for 49 of 51 cases (96.08%). For the 49 modifications, the cost savings totaled $98,750.64, for an average of $2015.32 saved per modification. This study provides evidence of the significant contribution of genetic counselors in a laboratory setting and demonstrates the benefit of laboratories working with ordering providers to identify the best test for their patients. The review of test orders by a genetic counselor both improves genetic test ordering strategies and decreases the amount of health care dollars spent on genetic testing.