Everolimus Through Plasmatic Concentrations in Cancer Patients: Prospective Longitudinal Observational Multicentric Study (DIANA-1 Project).

Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), is actually used to prevent organ transplant rejection and treat metastatic breast, renal, and neuroendocrine cancers. Despite significant pharmacokinetic variability among patients, routine therapeutic drug monitoring (TDM) is not commonly used in oncology. The aim of this multicenter, prospective observational cohort study is to assess the prevalence of everolimus minimum concentration at a steady state (Cminss) falling outside the therapeutic range (10-26.

Expanding the Clinical Spectrum of Variants: A Case Report on Non-Syndromic Retinal Dystrophy with a Mild Phenotype.

: Biallelic pathogenic variants in the gene are typically associated with severe, early-onset inherited retinal dystrophies (IRDs) in both syndromic and non-syndromic forms. This study explores the phenotypic variability of non-syndromic IRDs associated with variants, focusing on two siblings with biallelic variants, one of whom exhibits a remarkably mild phenotype, thereby expanding the clinical spectrum. : Whole-exome sequencing (WES) and mRNA analysis were performed to identify and characterize variants in the siblings.

Deciphering complexity: variants linked to an atypical retinal dystrophy phenotype.

exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered variant. Whole-exome sequencing was performed to identify potential causative variants.

Intermediate Repeat Expansion in the Gene as a Risk Factor in the ALS and FTD Spanish Population.

Intermediate CAG expansions in the gene ataxin-2 () are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in with the risk and phenotype of ALS and FTD in the Spanish population.

Novel intragenic deletion within the FXN gene in a patient with typical phenotype of Friedreich ataxia: may be more prevalent than we think?

Background: Friedreich ataxia is the most common inherited ataxia in Europe and is mainly caused by biallelic pathogenic expansions of the GAA trinucleotide repeat in intron 1 of the FXN gene that lead to a decrease in frataxin protein levels. Rarely, affected individuals carry either a large intragenic deletion or whole-gene deletion of FXN on one allele and a full-penetrance expanded GAA repeat on the other allele.

Case Presentation: We report here a patient that presented the typical clinical features of FRDA and genetic analysis of FXN intron 1 led to the assumption that the patient carried the common biallelic expansion.

Improving Hereditary Hemorrhagic Telangiectasia Molecular Diagnosis: A Referral Center Experience.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin () and activin A receptor type II-like 1 () genes are detected in more than 90% of the patients undergoing molecular testing. The identification of variants of unknown significance is often seen as a challenge in clinical practice that makes family screening and genetic counseling difficult.

Polygenic Risk of Hypertriglyceridemia Is Modified by BMI.

Background: Genetic risk scores (GRSs) have partially improved the understanding of the etiology of moderate hypertriglyceridemia (HTG), which until recently was mainly assessed by secondary predisposing causes. The main objective of this study was to assess whether this variability is due to the interaction between clinical variables and GRS. Methods: We analyzed 276 patients with suspected polygenic HTG.

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus.

SLE is associated with increased cardiovascular risk. The objective of this study was to determine the prevalence of asymptomatic carotid atherosclerosis to analyze its relationship with dyslipidemia and related genetic factors in a population of patients with SLE. Seventy-one SLE female patients were recruited.

Implication between Genetic Variants from APOA5 and ZPR1 and NAFLD Severity in Patients with Hypertriglyceridemia.

Background: Lipid metabolism disorders, especially hypertriglyceridemia (HTG), are risk factors for non-alcoholic fatty liver disease (NAFLD). However, the association between genetic factors related to HTG and the risk of NAFLD has been scarcely studied.

Methods: A total of 185 subjects with moderate HTG were prospectively included.

Precipitated sdLDL: An easy method to estimate LDL particle size.

Background: LDL-C lowering is the main measure in cardiovascular disease prevention but a residual risk of ischemic events still remains. Alterations of lipoproteins, specially, increase in small dense LDL (sdLDL) particles are related to this risk.

Objective: To investigate the potential use of sdLDL cholesterol concentration (sdLDL-C) isolated by an easy precipitation method and to assess the impact of a set of clinical and biochemical variables determined by NMR on sdLDL concentration.

KIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment.

Introduction: The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins.

Properties and units in the clinical laboratory sciences part XXIV. Properties and units in clinical molecular genetics (technical report 2017).

This document describes the application of the syntax, semantic rules, and format of the Nomenclature for Properties and Units (NPU) terminology for coded dedicated kinds-of-property in the subject field of clinical molecular genetics. A vocabulary for NPU definitions in this field, based on international terminology and nomenclature, is introduced; examples of actual NPU definitions for different types of investigations are given and explained.

ANRIL as a genetic marker for cardiovascular events in renal transplant patients - an observational follow-up cohort study.

Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplant recipients. Several single-nucleotide polymorphisms (SNPs) in the ANRIL gene pathway have been associated with cardiovascular events (CE). The main objective was to ascertain whether ANRIL (rs10757278) and CARD8 (rs2043211) SNPs could mediate susceptibility to CE.

APOE Variants E2, E3, and E4 Can Be Miscalled By Classical PCR-RFLP When The Christchurch Variant Is Also Present.

Background: The APOE Christchurch (APOECh) is a rare variant (c.543C>A) in codon 154. It was first described in an E2 patient with type III dyslipidemia, and thus initially called E2Ch.

HLA-B*57: 01 genotyping in the prevention of hypersensitivity to abacavir: 5 years of experience.

Introduction: Most of the cost-effectiveness analyses are based on estimations to make decisions on the future implementation of a test. However, the model should be verified with real data to prove that previous estimations have been successfully fulfilled.

Objective: To study the economic impact of the systematic HLA-B*57:01 genotyping in preventing hypersensitivity reactions (HSRs) in the patient population of a tertiary-care hospital treated with abacavir (ABC) using retrospective data of 5 years of experience.

Meeting report: present state of molecular genetics in clinical laboratories. Report on the VII European Symposium on Clinical Laboratory and In Vitro Diagnostic Industry in Barcelona.

The VII European Symposium of the Clinical Laboratory and In Vitro Diagnostic Industry, co-organized between the Catalan Association for Clinical Laboratory Sciences (ACCLC) and the Catalan Society of Biology, was held on May 28th-29th, 2013 in Barcelona (Catalonia, Spain) under the IFCC auspices and the IUPAC sponsorship. The subject of the present Symposium was "Molecular Genetics in the Clinical Laboratory" and began with an opening conference that was a stroll through the history of molecular genetics in the context of the clinical laboratory. The scientific program was structured in several 2-h length roundtables that dealt with the following topics: recent advances in molecular genetics for clinical microbiology, latest evidences and real applicability of pharmacogenetics in the clinical practice, quality assurance of a molecular genetics laboratory, and latest trends in prenatal genetic diagnosis.

Significance of a change between two consecutive measured values.

Background: The interpretation of a change between two consecutive measured values of a given quantity in the same patient is still controversial and it is not commonly found in clinical laboratory reports. We present here a manageable and affordable approach for all clinical laboratories to help physicians to interpret these differences.

Methods: We selected all pairs of two consecutive measured values of serum albumin concentration and serum thyrotropin concentration, both within the biological reference interval, delivered by our clinical laboratory in a 2-year period (2008-2009).