A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice.

Background: Despite the use of Next-Generation Sequencing (NGS) as the gold standard for the diagnosis of rare diseases, its clinical implementation has been challenging, limiting the cost-effectiveness of NGS and the understanding, control and safety essential for decision-making in clinical applications. Here, we describe a personalized NGS-based strategy integrating precision medicine into a public healthcare system and its implementation in the routine diagnosis process during a five-year pilot program.

Methods: Our approach involved customized probe designs, the generation of virtual panels and the development of a personalized medicine module (PMM) for variant prioritization.

Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene.

Background: Biallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which structural variants (SVs) represent a common cause of disease. However, their identification using short-read sequencing (SRS) is not always feasible.

Delving into the Role of lncRNAs in Papillary Thyroid Cancer: Upregulation of LINC00887 Promotes Cell Proliferation, Growth and Invasion.

Papillary thyroid carcinoma (PTC) is the most common histological category of thyroid cancer. In recent years, there has been an increasing number of studies on lncRNAs in PTC. Long intergenic non-protein coding RNA 887 (LINC00887) is a critical oncogene in developing other cancers.

Expanding the phenotype of : a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant.

Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders that often severely impair vision. Some patients manifest poor central vision as the first symptom due to cone-dysfunction, which is consistent with cone dystrophy (COD), Stargardt disease (STGD), or macular dystrophy (MD) among others. Here, we aimed to identify the genetic cause of autosomal dominant COD in one family.

Genetic profile in patients with complicated acute aortic syndrome: the GEN-AOR study.

Introduction And Objectives: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability.

Methods: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions.

Identification of a novel mutation in gene in mother and daughter with Kallmann syndrome.

Objectives: Congenital hypogonadotropic hypogonadism combined with anosmia or hyposmia is considered Kallmann syndrome (KS). It is often accompanied by bone defects.

Case Presentation: Here, we report a girl and her mother with KS caused by a novel mutation in the fibroblast growth factor receptor 1 gene ().

Air- and dustborne fungi in repositories of the National Archive of the Republic of Cuba.

This study has as objectives to determine the concentration and diversity of the air- and dustborne mycobiota in seven National Archive of the Republic of Cuba repositories, and to assess the potential risk of biodeterioration that isolated taxa may have. In the indoor and outdoor environmental microbiological samplings a SAS biocollector was used and the indoor/outdoor (I/O) ratio was determined for each repository. The settled dust was collected during six months.

A comprehensive WGS-based pipeline for the identification of new candidate genes in inherited retinal dystrophies.

To enhance the use of Whole Genome Sequencing (WGS) in clinical practice, it is still necessary to standardize data analysis pipelines. Herein, we aimed to define a WGS-based algorithm for the accurate interpretation of variants in inherited retinal dystrophies (IRD). This study comprised 429 phenotyped individuals divided into three cohorts.

Antimicrobial Resistance and Genetic Lineages of from Wild Rodents: First Report of C-Positive Methicillin-Resistant (MRSA) in Portugal.

The frequent carriage of , including methicillin-resistant (MRSA), by wild animals along with its zoonotic potential poses a public health problem. Furthermore, the repeated detection of the A gene homologue, C, in wildlife raises the question whether these animals may be a reservoir for C-MRSA. Thus, we aimed to isolate and MRSA from wild rodents living in port areas and to characterize their antimicrobial resistance and genetic lineages.

Atypical astroglial pTDP-43 pathology in astroglial predominant tauopathy.

We observed atypical astrocytic pTDP-43 pathology in astroglial predominant tauopathy.

Lipid remodeling in response to methionine stress in MDA-MBA-468 triple-negative breast cancer cells.

Methionine (Met) is an essential amino acid and critical precursor to the cellular methyl donor S-adenosylmethionine. Unlike nontransformed cells, cancer cells have a unique metabolic requirement for Met and are unable to proliferate in growth media where Met is replaced with its metabolic precursor, homocysteine. This metabolic vulnerability is common among cancer cells regardless of tissue origin and is known as "methionine dependence", "methionine stress sensitivity", or the Hoffman effect.

Effect of the oscillating magnetic field on airborne fungal.

This study shows that some species of fungi are affected by the magnetic field, which should be taken into account in studies of airborne fungal and air quality. The aim of this paper was to evaluate the effect of the oscillating magnetic field (OMF) on the behavior of colonies of three fungi genus growth in different culture mediums. The stains were: Aspergillus niger, Cladosporium cladosporioides and Penicillium citrinum and were inoculated in 90 mm Petri dishes with: Malt Extract Agar (MEA), Sabouraud Dextrose Agar (SDA) and Czapek-Dox Agar (CDA).

A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification.

The management of unsolved inherited retinal dystrophies (IRD) cases is challenging since no standard pipelines have been established. This study aimed to define a diagnostic algorithm useful for the diagnostic routine and to address unsolved cases. Here, we applied a Next-Generation Sequencing-based workflow, including a first step of panel sequencing (PS) followed by clinical-exome sequencing (CES) and whole-exome sequencing (WES), in 46 IRD patients belonging to 42 families.

A complementary study approach unravels novel players in the pathoetiology of Hirschsprung disease.

Hirschsprung disease (HSCR, OMIM 142623) involves congenital intestinal obstruction caused by dysfunction of neural crest cells and their progeny during enteric nervous system (ENS) development. HSCR is a multifactorial disorder; pathogenetic variants accounting for disease phenotype are identified only in a minority of cases, and the identification of novel disease-relevant genes remains challenging. In order to identify and to validate a potential disease-causing relevance of novel HSCR candidate genes, we established a complementary study approach, combining whole exome sequencing (WES) with transcriptome analysis of murine embryonic ENS-related tissues, literature and database searches, in silico network analyses, and functional readouts using candidate gene-specific genome-edited cell clones.

CSVS, a crowdsourcing database of the Spanish population genetic variability.

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes.

The V410L knockdown resistance mutation occurs in island and continental populations of Aedes aegypti in West and Central Africa.

The extensive use of insecticides for vector control has led to the development of insecticide resistance in Aedes aegypti populations on a global scale, which has significantly compromised control actions. Insecticide resistance, and its underlying mechanisms, has been investigated in several countries, mostly in South American and Asian countries. In Africa, however, studies reporting insecticide resistance are rare and data on resistance mechanisms, notably knockdown resistance (kdr) mutations, is scarce.

Unmasking Retinitis Pigmentosa complex cases by a whole genome sequencing algorithm based on open-access tools: hidden recessive inheritance and potential oligogenic variants.

Background: Retinitis Pigmentosa (RP) is a clinically and genetically heterogeneous disorder that results in inherited blindness. Despite the large number of genes identified, only ~ 60% of cases receive a genetic diagnosis using targeted-sequencing. The aim of this study was to design a whole genome sequencing (WGS) based approach to increase the diagnostic yield of complex Retinitis Pigmentosa cases.