Combining full-length gene assay and SpliceAI to interpret the splicing impact of all possible SPINK1 coding variants.

Background: Single-nucleotide variants (SNVs) within gene coding sequences can significantly impact pre-mRNA splicing, bearing profound implications for pathogenic mechanisms and precision medicine. In this study, we aim to harness the well-established full-length gene splicing assay (FLGSA) in conjunction with SpliceAI to prospectively interpret the splicing effects of all potential coding SNVs within the four-exon SPINK1 gene, a gene associated with chronic pancreatitis.

Results: Our study began with a retrospective analysis of 27 SPINK1 coding SNVs previously assessed using FLGSA, proceeded with a prospective analysis of 35 new FLGSA-tested SPINK1 coding SNVs, followed by data extrapolation, and ended with further validation.

An unusual diagnosis of alpha-mannosidosis with ocular anomalies: Behind the scenes of a hidden copy number variation.

Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder caused by biallelic mutations in the MAN2B1 gene and characterized by a wide clinical heterogeneity. Diagnosis for this multisystemic disorder is confirmed by the presence of either a deficiency in the lysosomal enzyme acid alpha-mannosidase or biallelic mutations in the MAN2B1 gene. This diagnosis confirmation is crucial for both clinical management and genetic counseling purposes.

Superior Pedicle Breast Reduction: Multivariate Analysis of Complication Risk Factors and Building a Predictive Score in 1306 Patients.

Background: Breast reduction surgery for hypertrophy is one of the most commonly performed procedures in plastic surgery. This surgery exposes patients to complications that are well-documented in the literature. The objective of this study is to identify risk factors to establish an estimate of the risk of developing complications.

Renal involvement is frequent in adults with primary mitochondrial disorders: an observational study.

Background: Mitochondrial functions are controlled by genes of both mitochondrial and nuclear DNA. Pathogenic variants affecting any of these are responsible for primary mitochondrial disorders (MIDs), which can be diagnosed during adulthood. Kidney functions are highly dependent on mitochondrial respiration.

Cutevariant: a standalone GUI-based desktop application to explore genetic variations from an annotated VCF file.

Summary: Cutevariant is a graphical user interface (GUI)-based desktop application designed to filter variations from annotated VCF file. The application imports data into a local SQLite database where complex filter queries can be built either from GUI controllers or using a domain-specific language called Variant Query Language. Cutevariant provides more features than existing applications and is fully customizable thanks to a complete plugins architecture.

Genetic features of the poxtA linezolid resistance gene in human enterococci from France.

Objectives: To describe the prevalence of poxtA among clinical linezolid-resistant enterococci (LRE) collected in France from 2016 to 2020 and to extensively characterize its genetic supports and environments.

Methods: All LRE clinical isolates received at the National Reference Centre for Enterococci from French hospitals between 2016 and 2020 were included. LRE isolates were screened for linezolid resistance genes (cfr-like, optrA and poxtA) by real-time PCR and phenotypically characterized.

and Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis.

Multiple osteochondromas (MO), the most common type of benign bone tumor, is an autosomal dominant skeletal disorder characterized by multiple cartilage-capped bony protuberances. In most cases, and , which encode glycosyltransferases involved in the biosynthesis of heparan sulfate, are the genes responsible. Here we describe the clinical, phenotypic and genetic characterization of MO in 22 unrelated Chinese families involving a total of 60 patients.

PharmFrag: An Easy and Fast Multiplex Pharmacogenetics Assay to Simultaneously Analyze 9 Genetic Polymorphisms Involved in Response Variability of Anticancer Drugs.

Regarding several cytotoxic agents, it was evidenced that genetic polymorphisms in genes encoding enzymes involved in their metabolism are associated with higher risk of toxicity. Genotyping these genes before treatment is a valuable strategy to prevent side effects and to predict individual response to drug therapy. This pharmacogenetic approach is recommended for chemotherapies such as thiopurines (azathioprine, 6-mercaptopurine, thioguanine), irinotecan, and fluoropyrimidines (capecitabine and 5-fluorouracil).

Non-Linear Pharmacokinetics of Oral Roscovitine (Seliciclib) in Cystic Fibrosis Patients Chronically Infected with : A Study on Population Pharmacokinetics with Monte Carlo Simulations.

Roscovitine (Seliciclib), a new protein kinase inhibitor, was administered orally to adult patients with cystic fibrosis for the first time in the ROSCO-CF trial, a dose-escalation, phase IIa, randomized, controlled trial. Extensive pharmacokinetic sampling was performed up to 12 h after the first oral dose. Roscovitine and its main metabolite M3 were quantified by liquid chromatography coupled with tandem mass spectrometry.

Molecular and functional analysis of the novel cfr(D) linezolid resistance gene identified in Enterococcus faecium.

Objectives: To characterize the novel cfr(D) gene identified in an Enterococcus faecium clinical isolate (15-307.1) collected from France.

Methods: The genome of 15-307.

B-cell and T-cell quantification in minor salivary glands in primary Sjögren's syndrome: development and validation of a pixel-based digital procedure.

Background: Evaluating lymphocytic infiltration of minor salivary gland biopsy in primary Sjögren's syndrome is challenging. We developed and evaluated a digital method for quantifying B and T lymphocytes in whole minor salivary gland biopsy slides.

Methods: Minor salivary gland biopsies were immunostained with anti-CD20/anti-CD3 antibodies using red/brown chromogens.