Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy.

Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.

Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium.

Examination of the Corneal Endothelium in Patients With Congenital Aniridia With a PAX6 Mutation Using In Vivo Confocal Laser Scanning Microscopy.

Purpose: In PAX6 syndrome, it is still not clear, whether prenatally, parallel to the iris tissue developmental anomaly, there is neural ectodermal, neural crest, or mesodermal cell deposition at the corneal endothelium, affecting endothelial structure and function. In addition, because of the postnatal corneal inflammation and commonly appearing secondary glaucoma, progressive endothelial changes are expected. Our purpose was to study the corneal endothelium in subjects with PAX6 aniridia, using in vivo confocal laser scanning microscopy.

Exploring non-coding variants and evaluation of antisense oligonucleotides for splicing redirection in Usher syndrome.

Exploring non-coding regions is increasingly gaining importance in the diagnosis of inherited retinal dystrophies. Deep-intronic variants causing aberrant splicing have been identified, prompting the development of antisense oligonucleotides (ASOs) to modulate splicing. We performed a screening of five previously described deep-intronic variants among monoallelic patients with Usher syndrome (USH) or isolated retinitis pigmentosa.

Technical challenges of intracellular flow cytometry-based assays as a functional complement to diagnosis of signaling defects of inborn errors of immunity: PI3K pathway as a case of study.

Background: The use of next-generation sequencing in inborn errors of immunity (IEI) has considerably increased the identification of novel gene variants, many of which are identified in patients without the described clinical phenotype or with variants of uncertain pathogenic significance in previously described genes. Properly designed functional and cellular assays, many necessarily accomplished by research-based laboratories, reveal the pathogenic consequences of the gene variants and contribute to diagnosis. Activated PI3Kδ syndrome (APDS) is a rare disease that can be divided into APDS1, caused by gain of function (GOF) mutations in gene, and APDS2, with loss of function (LOF) variants in the gene.

DNA Methylation Analysis by Bisulfite Pyrosequencing of Mouse Embryonic Fibroblasts with Reprogramming Enhanced by Thyroid Hormones.

DNA methylation is a widely studied epigenetic mark which in mammals involves the incorporation of a methyl group to the fifth carbon of cytosines, mainly those belonging to CpG dinucleotides. It has been linked to context-dependent regulatory functions ranging from gene and repetitive DNA silencing to gene body transcriptional activity. Because of its important roles during embryonic development and cell differentiation, DNA methylation can be used to track cell reprogramming by measuring the methylation levels of pluripotency-associated factors.

Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series.

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed.

Objectives: The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP.

Gestational breast cancer: distinctive molecular and clinico-epidemiological features.

Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6-15% of BC cases in women aged 20-44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012-03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC.

Cas9-targeted-based long-read sequencing for genetic screening of locus.

Introduction: Long-read sequencing (LRS) enables accurate structural variant detection and variant phasing. When a molecular diagnosis is suspected, target enrichment can reduce the cost and duration of sequencing.

Methods: LRS was conducted in five inherited retinal dystrophy (IRD) patients harboring a monoallelic variant in that remained uncharacterized after clinical exome sequencing (CES).

Overexpression of Glyoxalase 2 in Human Breast Cancer Cells: Implications for Cell Proliferation and Doxorubicin Resistance.

Glyoxalase 2 (Glo2) is an enzyme of the glyoxalase system whose pathway parallels glycolysis and which aims to remove methylglyoxal (MGO). This study analyzed the possible additional roles of the Glo2 enzyme in breast cancer (MCF7) and non-cancer (HDF) cell lines, investigating its presence at the nuclear level and its potential involvement in cell proliferation and chemotherapy resistance. The results revealed that Glo2 is overexpressed in cancer cells, and its expression is higher during the proliferative (S and G2/M) phases of the cell cycle.

The Key Features of a Genetic Nondiscrimination Policy: A Delphi Consensus Statement.

Importance: Governments worldwide have become increasingly cognizant of the spread of genetic discrimination (negative treatment or harm on the basis of actual or presumed genetic characteristics). Despite efforts by a number of governments to establish regulations addressing this phenomenon, public concern about genetic discrimination persists.

Objective: To identify key elements of an optimal genetic nondiscrimination policy and inform policymakers as they seek to allay genetic nondiscrimination and related public anxieties.

Discovery of New Highly Potent Histamine H Receptor Antagonists, Calcium Channel Blockers, and Acetylcholinesterase Inhibitors.

At present, one of the most promising strategies to tackle the complex challenges posed by Alzheimer's disease (AD) involves the development of novel multitarget-directed ligands (MTDLs). To this end, we designed and synthesized nine new MTDLs using a straightforward and cost-efficient one-pot Biginelli three-component reaction. Among these newly developed compounds, one particular small molecule, named has emerged as a promising MTDL.

Role of miRNA-mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell-cell adhesion, cardiomyocyte death and fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of arrhythmogenic cardiomyopathy. Moreover, signalling pathways such as Wnt/ß-catenin and transforming growth factor-β have been involved in the disease progression.

In Vitro Modulation of Autophagy by New Antioxidant Nitrones as a Potential Therapeutic Approach for the Treatment of Ischemic Stroke.

Stroke is a leading cause of death worldwide, yet current therapeutic strategies remain limited. Among the neuropathological events underlying this disease are multiple cell death signaling cascades, including autophagy. Recent interest has focused on developing agents that target molecules involved in autophagy to modulate this process under pathological conditions.

Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression.

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.

Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series.

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed.

Objectives: The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP.

Permselectivity of Silk Fibroin Hydrogels for Advanced Drug Delivery Neurotherapies.

A promising trend in tissue engineering is using biomaterials to improve the control of drug concentration in targeted tissue. These vehicular systems are of specific interest when the required treatment time window is higher than the stability of therapeutic molecules in the body. Herein, the capacity of silk fibroin hydrogels to release different molecules and drugs in a sustained manner was evaluated.

Navigating Dravet syndrome in Spain: A cross-sectional study of diagnosis, management, and care coordination.

Objectives: Dravet syndrome (DS) is a rare form of refractory epilepsy that begins in the first year of life. Approximately 85% of patients have a mutation in the SCN1A gene, which encodes a voltage-gated sodium channel. The main objective of the present work was to assess the degree of knowledge of DS among Spanish primary care (PC) professionals, the communication flow between them and the pediatric neurologists (PNs), and the services available and resources offered to patients in Spain when searching for a diagnosis and adequate treatment.