Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.     

Attenuation of FLOWERING LOCUS C activity as a mechanism for the evolution of summer-annual flowering behavior in Arabidopsis

Plant species have evolved a wide variety of flowering habits, each adapted to maximize reproductive success in their local environment. Even within a species, accessions from different environments can exhibit markedly different flowering behavior. In Arabidopsis, some accessions are rapid-cycling summer annuals, whereas others accessions are late flowering and vernalization responsive and thus behave as winter annuals. Two genes, FLOWERING LOCUS C (FLC) and FRIGIDA (FRI), interact synergistically to confer the winter-annual habit. Previous work has shown that many summer-annual accessions contain null mutations in the FRI gene; thus it appears that these summer-annual accessions have arisen from winter-annual ancestors by losing FRI function. In this work we demonstrate that naturally occurring allelic variation in FLC has provided another route to the evolution of summer-annual flowering behavior in Arabidopsis. We have identified two summer-annual accessions, Da (1)-12 and Shakhdara, that contain functional alleles of FRI, but are early flowering because of weak alleles of FLC. We have also determined that the weak allele of FLC found in Landsberg erecta is naturally occurring. Unlike accessions that have arisen because of loss-of-function mutations in FRI, the FLC alleles from Da (1)-12, Shakhdara, and Landsberg erecta are not nulls; however, they exhibit lower steady-state mRNA levels than strong alleles of FLC. Sequence analysis indicates that these weak alleles of FLC have arisen independently at least twice during the course of evolution.     

Sleep in Type 1 Diabetes: Implications for Glycemic Control and Diabetes Management

Purpose of Review

To highlight recent findings from studies of sleep in type 1 diabetes (T1D), with a focus on the role of sleep in self-management, the cognitive and psychosocial outcomes related to sleep disturbances, and factors associated with sleep disturbances specific to T1D.

Recent Findings

People with T1D experience higher rates of sleep disturbances than people without diabetes, and these disturbances have negative implications for glycemic control and diabetes management, as well as psychosocial and cognitive outcomes. Inconsistent sleep timing (bedtime and wake time) has emerged as a potential target for interventions, as variability in sleep timing has been linked with poorer glycemic control and adherence to treatment. Sleep-promoting interventions and new diabetes technology have the potential to improve sleep in people with T1D.

Summary

Sleep is increasingly considered a critical factor in diabetes management, but more multi-method and longitudinal research is needed. We emphasize the importance of sufficient and consistent sleep for people with T1D, and the need for providers to routinely assess sleep among patients with T1D.

     

Influenza: the reemergence of an ancient disease and its risk of pandemia

Influenza is a seasonally, acute respiratory disease, highly transmissible. The diversity of the natural reservoirs of influenza A virus and its faculty of reassortment increase the risk of a new pandemia. Prevention strategies during the outbreaks include vaccination indicated to risk population as infants between 6 to 2 years old, persons above 65 years old, pregnant women and patients with underlying diseases. Antiviral prophylaxis is useful to control small outbreaks and to be used in household contacts of risk population who have not been vaccinated. Antiviral drugs as a treatment should be considered in persons with severe disease. During a pandemia these prevention measures must be reinforced and rational use of antiviral drugs and vaccine with the pandemic strain should be emphasized.     

Screening for primary aldosteronism in a cohort of Brazilian patients with resistant hypertension

The objective was to estimate the prevalence of plasma aldosterone concentration:plasma renin activity ratio >30 ng/dL:ng/mL/h in patients with resistant hypertension and to describe the computed tomography findings of adrenal glands in those with elevated ratios. In a cross-sectional design, 492 patients were enrolled. All patients with plasma aldosterone concentration:plasma renin activity ratio >or=30 ng/dL:ng/mL/h (n=77) underwent abdominal computed tomography. Patients with an adrenal image of possible aldosterone-producing adenoma underwent a saline-loading test. The prevalence of elevated plasma aldosterone concentration:plasma renin activity ratio was 15.7% (95% confidence interval, 12.6-19.2). Twelve patients showed adrenal abnormalities on computed tomography. The level of renin was low in 50% of the sample. Results indicate a low prevalence of aldosterone-producing adenoma. Our evidence points out the importance of confirming the hypothesis that essential hypertension, low-renin hypertension, and idiopathic hyperaldosteronism could be the same disease, but at different neurohormonal stages, and aldosterone-producing adenoma may be yet another disease.