Dominant or recessive mutations in the RYR1 gene causing central core myopathy in Brazilian patients

Central Core Disease (CCD) is an inherited neuromuscular disorder characterized by the presence of cores in muscle biopsy. CCD is caused by mutations in the RYR1 gene. This gene encodes the ryanodine receptor 1, which is an intracellular calcium release channel from the sarcoplasmic reticulum to the cytosol in response to depolarization of the plasma membrane. Mutations in this gene are also associated with susceptibility to Malignant Hyperthermia (MHS).In this study, we evaluated 20 families with clinical and histological characteristics of CCD to identify primary mutations in patients, for diagnosis and genetic counseling of the families.We identified variants in the RYR1 gene in 19/20 families. The molecular pathogenicity was confirmed in 16 of them. Most of these variants (22/23) are missense and unique in the families. Two variants were recurrent in two different families. We identified six families with biallelic mutations, five compound heterozygotes with no consanguinity, and one homozygous, with consanguineous parents, resulting in 30% of cases with possible autosomal recessive inheritance. We identified seven novel variants, four of them classified as pathogenic. In one family, we identified two mutations in exon 102, segregating in cis, suggesting an additive effect of two mutations in the same allele.This work highlights the importance of using Next-Generation Sequencing technology for the molecular diagnosis of genetic diseases when a very large gene is involved, associated to a broad distribution of the mutations along it. These data also influence the prevention through adequate genetic counseling for the families and cautions against malignant hyperthermia susceptibility.Key words: central core disease, RYR1, Next Generation Sequencing     

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

Findings on magnetic resonance imaging of idiopathic right ventricular outflow tachycardia

We evaluated 20 patients with idiopathic ventricular tachycardia for structural abnormalities using magnetic resonance imaging (MRI) and compared them with 20 controls. Two experienced observers interpreted the MRIs. There were no differences in incidence of qualitative MRI findings in patients compared with controls. These findings do not favor an association between anatomic abnormalities and arrhythmia in these patients.     

Successful RF ablation of permanent VT in a patient with acute coronary syndrome treated by complex angioplasty and stent implantation

We describe a case of a 59-year-old male with permanent VT in the course of an acute coronary syndrome. Coronary angiography revealed acute occlusion of the right coronary artery. Although the underlying condition was treated by implantation of 4 stents with excellent haemodynamic effect (TIMI 3), the tachycardia continued, being refractory to drugs (amiodarone). The attempts to restore sinus rhythm by DC electrical cardioversion or transvenous pacing were unsuccessful. The patient was referred to the EP lab. A critical isthmus localised at the paraseptal region of the LV and parallel to the mitral annulus was identified. The isthmus was closed by linear RF application, resulting in VT termination. Due to impaired LV ejection fraction (<30%) the patient was scheduled for ICD implantation. During 6-week follow-up the patient remained free of arrhythmia.     

Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model

OBJECTIVES: To identify an accurate and reproducible method to define myocardial infarct (MI) size, we conducted a study in a closed-chest canine model of acute myocardial infarction, in which MI size was measured using different thresholding techniques and by imaging at different delay times after contrast administration. BACKGROUND: The MI size by contrast-enhanced magnetic resonance imaging (CE-MRI) is directly related to long-term prognosis. However, previous measurements were done using nonuniform methods and tended to overestimate nonviable areas. METHODS: Thirteen animals underwent 90 min of coronary artery occlusion, followed by reperfusion. The CE-MRI data were acquired within 24 h after reperfusion and compared with triphenyltetrazolium chloride pathology. In the first nine animals, images were obtained approximately 15 min after gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) using an inversion-recovery gradient-echo pulse sequence. To identify the most accurate method, MI size by CE-MRI was measured visually and by semi-automatic thresholding techniques, using different criteria. In four additional animals, images were acquired every 6 min until 30 min after Gd-DTPA. RESULTS: Postmortem MI size was 13.5 +/- 2.6% of left ventricular volume. Semi-automatic techniques, using full-width at half-maximum (FWHM) criterion, correlated best with postmortem data (r(2) = 0.94, p < 0.001; results confirmed by Bland-Altman plots). Using FWHM, there was no difference in MI size between different delay times after contrast (15.2 +/- 2.9% to 14.5 +/- 4.2% at 6 and 30 min, respectively; p = NS). CONCLUSIONS: When an objective technique is used to define MI size by CE-MRI, accurate infarct size measurements can be obtained from images obtained up to 30 min after contrast administration.     

Isolation and characterization of 8 polymorphic microsatellite markers from the Greater Short-horned Lizard (Phrynosoma hernandesi)

The Greater Short-horned Lizard (Phrynosoma hernandesi) is a small reptile endemic to western North America that is classified as endangered in Canada. Here, we describe the development of 8 microsatellite markers for P. hernandesi. Observed allelic diversity varied from 2 to 11 while observed heterozygosity and expected heterozygosity ranged from 0.370–0.852 to 0.486–0.856, respectively. These markers will facilitate studies that address conservation of the species, such as levels of genetic diversity and population structure.     

Taxonomical Associative Memory

Assigning categories to objects allows the mind to code experience by concepts, thus easing the burden in perceptual, storage, and reasoning processes. Moreover, maximal efficiency of cognitive resources is attained with categories that best mirror the structure of the perceived world. In this work, we will explore how taxonomies could be represented in the brain, and their application in learning and recall. In a recent work, Sacramento and Wichert (in Neural Netw 24(2):143–147, 2011) proposed a hierarchical arrangement of compressed associative networks, improving retrieval time by allowing irrelevant neurons to be pruned early. We present an extension to this model where superordinate concepts are encoded in these compressed networks. Memory traces are stored in an uncompressed network, and each additional network codes for a taxonomical rank. Retrieval is progressive, presenting increasingly specific superordinate concepts. The semantic and technical aspects of the model are investigated in two studies: wine classification and random correlated data.     

Characterization of fifteen microsatellite markers for the kelp Laminaria ochroleuca and cross species amplification within the genus

The brown algal genus Laminaria (Phaeophyceae, Laminariales) is ecologically and economically important. Laminaria ochroleuca is the genus member with the southernmost distribution in the Northern hemisphere, from Southern Great Britain to Morocco. Here we describe the characterization of 15 microsatellite loci that can be used to study genetic diversity at different spatial scales and its dynamics in declining southern populations. These loci identified a number of alleles ranging from 3 to 26 (mean = 9). Expected heterozygosities range from 0.0824 to 0.9401. We also tested cross-amplification of these microsatellite markers in two other species within the genus, L. hyperborea and L. digitata. A total of eight and ten alleles cross-amplified in L. hyperborea and L. digitata, respectively. These 15 variable microsatellite loci are an important molecular tool to conduct population genetics studies in L. ochroleuca and other species within the genus.     

Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

相似文献