Search results for "Myopathies"

Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy

2019

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Substantial deficiency of free sialic acid in muscles of patients with GNE myopathy and in a mouse model

2017

GNE myopathy (GNEM), also known as hereditary inclusion body myopathy (HIBM), is a late- onset, progressive myopathy caused by mutations in the GNE gene encoding the enzyme responsible for the first regulated step in the biosynthesis of sialic acid (SA). The disease is characterized by distal muscle weakness in both the lower and upper extremities, with the quadriceps muscle relatively spared until the late stages of disease. To explore the role of SA synthesis in the disease, we conducted a comprehensive and systematic analysis of both free and total SA levels in a large cohort of GNEM patients and a mouse model. A sensitive LC/MS/MS assay was developed to quantify SA in serum and muscle h…

Analysis on sarcoglycans expression as markers of septic cardiomyopathy in sepsis-related death

2018

The post-mortem assessment of sepsis-related death can be carry out by many methods recently suggested as microbiological and biochemical investigations. In these cases, the cause of death is a multiple organ dysfunction due to a dysregulated inflammatory response occurring after the failure of infection control process. It was highlighted also that the heart can be a target organ in sepsis which determines the so-called septic cardiomyopathy characterized by myocardial depression. Several mechanisms to explain the pathophysiology of septic cardiomyopathy were suggested, but very few studies about the structural alterations of cardiac cells responsible for myocardial depression were carried…

The EP300/TP53 pathway, a suppressor of the Hippo and canonical WNT pathways, is activated in human hearts with arrhythmogenic cardiomyopathy in the …

2021

Aim Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure. Methods and results Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and 5 control samples were analyzed by RNA-S…

Complications of Diabetes 2017

2018

A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine

2018

ObjectiveTo describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified.MethodsPatients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed.ResultsEighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BIN1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confi…

Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure etiology and correlates to clinical variables.

2012

Downregulation of β1- adrenergic receptors (β1-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α1A, α1B, α1D, β1, β2, and β3) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients wit…

Protein aggregation in congenital myopathies.

2011

Protein aggregation in congenital myopathies may be encountered among different myofibrillar myopathies such as granulofilamentous myopathy, cytoplasmic body myopathy, or spheroid body myopathy, which are designated as αB crystallinopathy, desminopathy, and myotilinopathy, respectively, according to the respective mutant proteins. Caps in cap disease and reducing bodies in reducing body myopathy were disclosed to contain numerous proteins. The multitude of diverse proteins aggregating within muscle fibers suggests impaired extralysosomal degradation of proteins, a disturbance of catabolism. The lack of different proteins accruing, but the mutant ones at an early age of affected patients in …

Cardiac Magnetic Resonance with Delayed Enhancement of the Right Ventricle in patients with Left Ventricle primary involvement: diagnosis and evaluat…

2020

: Cardiac Magnetic Resonance (CMR) allows an accurate Right Ventricle (RV) assessment that could be of great relevance in diseases causing inflammation or fibrosis. The aim of this study was to evaluate the concomitant involvement of the RV in patients with delayed enhancement (DE) of the Left Ventricle (LV-DE) using CMR. We retrospectively enrolled 95 (male n. 66; age 55±18years; BMI 26±5kg/m2) consecutive patients with LV-DE who underwent a CMR (Achieva 1.5 T, Philips) for different indications: post-ischemic dilated cardiopathy (PDM), hypertrophic cardiomyopathy (HCM), myocardial infarction (MI), myocarditis/pericarditis (MP) and congenital heart disease (CD). We assessed the presence an…

Cardiomyopathy due to PRDM16 mutation: First description of a fetal presentation, with possible modifier genes

2020

PRDM16 (positive regulatory domain 16) is localized in the critical region for cardiomyopathy in patients with deletions of chromosome 1p36, as defined by Gajecka et al., American Journal of Medical Genetics, 2010, 152A, 3074-3083, and encodes a zinc finger transcription factor. We present the first fetal case of left ventricular non-compaction (LVNC) with a PRDM16 variant. The third-trimester obstetric ultrasound revealed a hydropic fetus with hydramnios and expanded hypokinetic heart. After termination of pregnancy, foetopathology showed a eutrophic fetus with isolated cardiomegaly. Endocardial fibroelastosis was associated with non-compaction of the myocardium of the left ventricle. Exom…