A new homozygous missense variant in LMOD3 gene causing mild nemaline myopathy with prominent facial weakness.

Nemaline myopathy (NEM) type 10, caused by biallelic mutations in LMOD3, is a severe congenital myopathy clinically characterized by generalized hypotonia and muscle weakness, respiratory insufficiency, joint contractures, and bulbar weakness. Here, we describe a family with two adult patients presenting mild nemaline myopathy due to a novel homozygous missense variant in LMOD3. Both patients presented mild delayed motor milestones, frequent falls during infancy, prominent facial weakness and mild muscle weakness in the four limbs.

VIsoQLR: an interactive tool for the detection, quantification and fine-tuning of isoforms in selected genes using long-read sequencing.

DNA variants altering the pre-mRNA splicing process represent an underestimated cause of human genetic diseases. Their association with disease traits should be confirmed using functional assays from patient cell lines or alternative models to detect aberrant mRNAs. Long-read sequencing is a suitable technique to identify and quantify mRNA isoforms.

Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models.

Cerebral ischemia is a condition affecting an increasing number of people worldwide, and the main cause of disability. Current research focuses on the search for neuroprotective drugs for its treatment, based on the molecular targets involved in the ischemic cascade. Nitrones are potent antioxidant molecules that can reduce oxidative stress.

Biallelic intragenic tandem duplication of CPLANE1 in Joubert syndrome: A case report.

Joubert syndrome (JS) is a clinically and genetically heterogeneous genetic disorder. To date, 40 JS-causing genes have been reported and CPLANE1 is one of the most frequently mutated, with biallelic pathogenic missense and truncating variants explaining up to 14% of JS cases. We present a case of JS diagnosed after the identification of a novel biallelic intragenic duplication of exons 20-46 of CPLANE1.

Prioritization of New Candidate Genes for Rare Genetic Diseases by a Disease-Aware Evaluation of Heterogeneous Molecular Networks.

Screening for pathogenic variants in the diagnosis of rare genetic diseases can now be performed on all genes thanks to the application of whole exome and genome sequencing (WES, WGS). Yet the repertoire of gene-disease associations is not complete. Several computer-based algorithms and databases integrate distinct gene-gene functional networks to accelerate the discovery of gene-disease associations.

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids.

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR.

Minigene Splicing Assays and Long-Read Sequencing to Unravel Pathogenic Deep-Intronic Variants in in Congenital Aniridia.

PAX6 haploinsufficiency causes aniridia, a congenital eye disorder that involves the iris, and foveal hypoplasia. Comprehensive screening of the PAX6 locus, including the non-coding regions, by next-generation sequencing revealed four deep-intronic variants with potential effects on pre-RNA splicing. Nevertheless, without a functional analysis, their pathogenicity could not be established.

The Endothelial Glycocalyx and Neonatal Sepsis.

Sepsis carries a substantial risk of morbidity and mortality in newborns, especially preterm-born neonates. Endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the vascular endothelium, with important vascular barrier function and cell adhesion properties, serving also as a mechano-sensor for blood flow. eGC shedding is recognized as a fundamental pathophysiological process generating microvascular dysfunction, which in turn contributes to multiple organ failure and death in sepsis.

Long Non-Coding RNAs as Epigenetic Regulators of Immune Checkpoints in Cancer Immunity.

In recent years, cancer treatment has undergone significant changes, predominantly in the shift towards immunotherapeutic strategies using immune checkpoint inhibitors. Despite the clinical efficacy of many of these inhibitors, the overall response rate remains modest, and immunotherapies for many cancers have proved ineffective, highlighting the importance of knowing the tumor microenvironment and heterogeneity of each malignancy in patients. Long non-coding RNAs (lncRNAs) have attracted increasing attention for their ability to control various biological processes by targeting different molecular pathways.

Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies.

Background: Limb-girdle muscular dystrophy (LGMD) is a rare neuromuscular disease including a growing and heterogeneous number of subtypes with variable phenotype. Their clinical and histopathological characteristics frequently overlap with other neuromuscular dystrophies. Our goal was to identify, by a non-invasive method, a molecular signature including biochemical and epigenetic parameters with potential value for patient prognosis and stratification.

The study of neural antibodies in neurology: A practical summary.

The field of Autoimmune Neurology is expanding rapidly, with new neural antibodies being identified each year. However, these disorders remain rare. Deciding when to test for these antibodies, when and what samples are to be obtained, how to handle and study them correctly, and how to interpret test results, is complex.

A Novel PiRNA Enhances CA19-9 Sensitivity for Pancreatic Cancer Identification by Liquid Biopsy.

Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element-induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis.

Benzochromenopyrimidines: Synthesis, Antiproliferative Activity against Colorectal Cancer and Physicochemical Properties.

Ten new differently substituted 3-benzyl-5-aryl-3,5-dihydro-4-benzo[6,7]chromeno[2,3-]pyrimidin-4,6,11-triones were synthesized by a simple and cost-efficient procedure in a one-pot, three-component reaction from readily available ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4-benzo[]chromene-3-carboxylates, benzylamine and triethyl orthoformate under solvent- and catalyst-free conditions. All the new compounds were screened for their antiproliferative activity against two colorectal-cancer-cell lines. The results showed that the compounds 3-benzyl-5-phenyl-3,5-dihydro-4-benzo[6,7]chromeno[2,3-]pyrimidine-4,6,11-trione () and 3-benzyl-5-(3-hydroxyphenyl)-3,5-dihydro-4-benzo[6,7]chromeno[2,3-]pyrimidine-4,6,11-trione () exhibited the most potent balanced inhibitory activity against human LoVo and HCT-116 cancer cells.

Androgen receptor polyQ alleles and COVID-19 severity in men: A replication study.

Background: Ample evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity.

-Hydroxy--Propargylamide Derivatives of Ferulic Acid: Inhibitors of Cholinesterases and Monoamine Oxidases.

Alzheimer's disease (AD) is a complex disorder characterized by impaired neurotransmission in cholinergic and monoaminergic neurons, which, in combination with the accumulation of misfolded proteins and increased oxidative stress, leads to the typical features of the disease at the biomolecular level. Given the limited therapeutic success of approved drugs, it is imperative to explore rationally supported therapeutic approaches to combat this disease. The search for novel scaffolds that bind to different receptors and inhibit AD disease-related enzymes could lead to new therapeutic solutions.

Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout.

Objective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout.

Methods: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease.

Polyfunctionalized α-Phenyl-tert-butyl(benzyl)nitrones: Multifunctional Antioxidants for Stroke Treatment.

Nowadays, most stroke patients are treated exclusively with recombinant tissue plasminogen activator, a drug with serious side effects and limited therapeutic window. For this reason, and because of the known effects of oxidative stress on stroke, a more tolerable and efficient therapy for stroke is being sought that focuses on the control and scavenging of highly toxic reactive oxygen species by appropriate small molecules, such as nitrones with antioxidant properties. In this context, herein we report here the synthesis, antioxidant, and neuroprotective properties of twelve novel polyfunctionalized α-phenyl--butyl(benzyl)nitrones.

Impact of cytomegalovirus infection prior to hematopoietic stem cell transplantation in children with inborn errors of immunity.

Unlabelled: The presence of active viral infections has an impact on the prognosis of patients undergoing hematopoietic stem cell transplantation (HSCT). Nevertheless, the number of reports of cytomegalovirus infection in patients with inborn errors of immunity (IEI) who undergo HSCT is relatively low. To analyze the effect of cytomegalovirus infection acquired prior to curative treatment on patient survival in 123 children with IEI.

Norovirus-associated White Matter Injury in a Term Newborn With Seizures.

Neonatal seizures with white matter injury have been associated with rotavirus, enterovirus and parechovirus. Neurological symptoms caused by norovirus have been occasionally reported in older children. We describe a case of a neonate with seizures and white matter lesions, with detection of human norovirus in stool samples from the patient and her mother.