Implementation of long-read sequencing for routine molecular diagnosis of familial mediterranean fever.

Background: Long-read sequencing technology, widely used in research, is proving useful in clinical diagnosis, especially for infectious diseases. Despite recent advances, it hasn't been routinely applied to constitutional human diseases. Long-read sequencing detects intronic variants and phases variants, crucial for identifying recessive diseases.

Exome-First Strategy in Adult Patients With CKD: A Cohort Study.

Introduction: Exome sequencing (ES) has widened the field of nephrogenomics in adult nephrology. In addition to reporting the diagnostic yield of ES in an adult cohort study, we investigated the clinical implications of molecular diagnosis and developed a clinical score to predict the probability of obtaining positive result.

Methods: From September 2018 we have used ES to prospectively perform a first-tier liberal exploration of adult nephropathies of unknown origin and/or when a genetic kidney disease was clinically suggested.

A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia.

Genetic diagnosis of familial hypercholesterolemia (FH) remains unexplained in 30 to 70% of patients after exclusion of monogenic disease. There is now a growing evidence that a polygenic burden significantly modulates LDL-cholesterol (LDL-c) concentrations. Several LDL-c polygenic risk scores (PRS) have been set up.

CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants.

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry missense variants of uncertain significance (VUS).

Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia.

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the (apolipoprotein B) and genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis.

Development of a new expanded next-generation sequencing panel for genetic diseases involved in dyslipidemia.

The aim of this study was to provide an efficient tool: reliable, able to increase the molecular diagnosis performance, to facilitate the detection of copy number variants (CNV), to assess genetic risk scores (wGRS) and to offer the opportunity to explore candidate genes. Custom SeqCap EZ libraries, NextSeq500 sequencing and a homemade pipeline enable the analysis of 311 dyslipidemia-related genes. In the training group (48 DNA from patients with a well-established molecular diagnosis), this next-generation sequencing (NGS) workflow showed an analytical sensitivity >99% (n = 532 variants) without any false negative including a partial deletion of one exon.

New psychoactive substances in oral fluid of drivers around a music festival in south-west France in 2017.

Driving under the influence of drugs (DUID) is a worldwide problem with potentially major forensic and life-threatening consequences. Although it is obvious that new psychoactive substances (NPS) could lead to impaireddriving, the prevalence of NPS use in a DUID context is unknown as the applied roadside screening tests for drugs of abuse (DOA) are not adapted for NPS detection. This works aims to tested oral fluid (OF) specimens for NPS in French drivers circulating around two music festivals (Artsenik 2017 and Garorock 2017) in order to assess the prevalence of consumption and the kind of used NPS in this particular population.

LSD Detection and Interpretation in Hair.

Lysergic acid diethylamide (LSD) is a powerful hallucinogen, active at very low dosages, with, as a direct consequence, potential difficulties to be detected and quantified in a clinical or forensic context, in body fluids and even more in hair. The aim of this work is to review literature data related to hair analysis of LSD with a particular focus on the main issues encountered in LSD detection in hair. Results of LSD investigation in hair remain difficult to interpret regarding the very sparse data available on LSD concentrations in hair (n=10).