Long-read genome sequencing identifies cryptic structural variants in congenital aniridia cases.

Background: Haploinsufficiency of the transcription factor PAX6 is the main cause of congenital aniridia, a genetic disorder characterized by iris and foveal hypoplasia. 11p13 microdeletions altering PAX6 or its downstream regulatory region (DRR) are present in about 25% of patients; however, only a few complex rearrangements have been described to date. Here, we performed nanopore-based whole-genome sequencing to assess the presence of cryptic structural variants (SVs) on the only two unsolved "PAX6-negative" cases from a cohort of 110 patients with congenital aniridia after unsuccessfully short-read sequencing approaches.

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.

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.

Fine Breakpoint Mapping by Genome Sequencing Reveals the First Large X Inversion Disrupting the Gene in a Patient with Syndromic Cataracts.

Inversions are structural variants that are generally balanced. However, they could lead to gene disruptions or have positional effects leading to diseases. Mutations in the gene cause Nance-Horan syndrome, an X-linked disorder characterised by congenital cataracts and dental anomalies.

Activation of cryptic donor splice sites by non-coding and coding variants contributes to congenital aniridia.

Background: The paired-domain transcription factor paired box gene 6 (PAX6) causes a wide spectrum of ocular developmental anomalies, including congenital aniridia, Peters anomaly and microphthalmia. Here, we aimed to functionally assess the involvement of seven potentially non-canonical splicing variants on missplicing of exon 6, which represents the main hotspot region for loss-of-function variants.

Methods: By locus-specific analysis of using Sanger and/or targeted next-generation sequencing, we screened a Spanish cohort of 106 patients with -related diseases.

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG.

Transient Expression in Islets During Pregnancy Correlates With β-Cell Survival, Revealing a Novel Candidate Gene in Gestational Diabetes Mellitus.

Transient expression was reported in mouse islets during gestation, whereas a genome-wide linkage and admixture mapping study highlighted as a candidate gene for diabetes mellitus (DM). We sought the significance of PAX8 expression in mouse and human islet biology. was induced in gestating mouse islets and in human islets treated with recombinant prolactin.

Chitosan-based coatings in the prevention of intravascular catheter-associated infections.

Central venous access devices play an important role in patients with prolonged intravenous administration requirements. In the last years, the coating of these devices with bactericidal compounds has emerged as a potential tool to prevent bacterial colonization. Our study describes the modification of 3D-printed reservoirs and silicone-based catheters, mimicking central venous access devices, through different approaches including their coating with the well known biocompatible and bactericidal polymer chitosan, with the anionic polysaccharide alginate; also, plasma treated surfaces were included in the study to promote polymer adhesion.

[Affective syndromes in liver transplant recipients: ¿mediated neurotoxicity immunosuppressive?].

Introduction: The onset of affective and psychotic in liver transplant patients symptoms, raises the need to explore the possible etiologies of mental symptoms.

Methodology: Case report and literature review.

Results: Four clinical cases of patients undergoing orthotopic liver transplantation, who in the early post transplant showed affective symptoms, delusions and psychomotor agitation for which they needed psychiatric hospitalization and treatment with psychotropic drugs are presented.

[Predominant polarity in type-I bipolar patients: Study in an isolated population with a high prevalence of mood disorders].

Introduction: Recent studies have shown that the predominant description of polarity has effects upon early detection and the timely beginning of treatment in patients with bipolar affective disorder (BAD).

Methodology: Cross sectional cut and descriptive study in 101 BAD patients coming from a genetically isolated population from the Colombian Region of Antioquia.

Results: The study covered a population of 101 patients with type-I BAD diagnosis, out of which 57,4% met the criteria for maniac polarity (MP), 10,1% exhibited depressive polarity (DP) and 25,7% were classified with Indefinite Polarity (IP).