The suitable prescription of the thyroid blood test in the diagnosis of dysthyroidism: a retrospective study in Rouen University Hospital

International audienc

Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome

International audienc

Patients with 10q22.3q23.1 recurrent deletion syndrome are at risk for juvenile polyposis

International audienc

Assessment of Multiplex Digital Droplet RT-PCR as a Diagnostic Tool for SARS-CoV-2 Detection in Nasopharyngeal Swabs and Saliva Samples

Abstract Background Reverse transcription-quantitative PCR on nasopharyngeal swabs is currently the reference COVID-19 diagnosis method but exhibits imperfect sensitivity. Methods We developed a multiplex reverse transcription-digital droplet PCR (RT-ddPCR) assay, targeting 6 SARS-CoV-2 genomic regions, and evaluated it on nasopharyngeal swabs and saliva samples collected from 130 COVID-19 positive or negative ambulatory individuals, who presented symptoms suggestive of mild or moderate SARS-CoV2 infection. Results For the nasopharyngeal swab samples, the results obtained using the 6-plex RT-ddPCR and RT-qPCR assays were all concordant. The 6-plex RT-ddPCR assay was more sensitive than RT-qPCR (85% versus 62%) on saliva samples from patients with positive nasopharyngeal swabs. Conclusion Multiplex RT-ddPCR represents an alternative and complementary tool for the diagnosis of COVID-19, in particular to control RT-qPCR ambiguous results. It can also be applied to saliva for repetitive sampling and testing individuals for whom nasopharyngeal swabbing is not possible. </jats:sec

Assessment of multiplex digital droplet RT-PCR as an accurate diagnosis tool for SARS-CoV-2 detection in nasopharyngeal swabs and saliva samples

ABSTRACTRT-qPCR on nasopharyngeal swabs is currently the reference COVID-19 diagnosis method. We developed a multiplex RT-ddPCR assay, targeting six SARS-CoV-2 genomic regions, and evaluated it on nasopharyngeal swabs and saliva samples collected from 130 COVID-19 positive or negative ambulatory individuals, who presented symptoms suggestive of mild or moderate Sars-CoV2 infection. The 6-plex RT-ddPCR assay was shown to have 100% sensitivity on nasopharyngeal swabs and a higher sensibility than RT-qPCR on saliva (85% versus 62%). Saliva samples from 2 individuals with negative results on nasopharyngeal swabs were found to be positive. These results show that multiplex RT-ddPCR should represent an alternative and complementary tool for the diagnosis of COVID-19, in particular to control RT-qPCR ambiguous results, and its application to saliva an appropriate strategy for repetitive sampling and testing individuals for whom nasopharyngeal swabbing is not possible.</jats:p

Copy Number Variants in miR-138 as a Potential Risk Factor for Early-Onset Alzheimer’s Disease

International audienceEarly-onset Alzheimer’s disease (EOAD) accounts for 5-10% of all AD cases, with a heritability ranging between 92% to 100%. With the exception of rare mutations in APP, PSEN1, and PSEN2 genes causing autosomal dominant EOAD, little is known about the genetic factors underlying most of the EOAD cases. In this study, we hypothesized that copy number variations (CNVs) in microRNA (miR) genes could contribute to risk for EOAD. miRs are short non-coding RNAs previously implicated in the regulation of AD-related genes and phenotypes. Using whole exome sequencing, we screened a series of 546 EOAD patients negative for autosomal dominant EOAD mutations and 597 controls. We identified 86 CNVs in miR genes of which 31 were exclusive to EOAD cases, including a duplication of the MIR138-2 locus. In functional studies in human cultured cells, we could demonstrate that miR-138 overexpression leads to higher Aβ production as well as tau phosphorylation, both implicated in AD pathophysiology. These changes were mediated in part by GSK-3β and FERMT2, a potential risk factor for AD. Additional disease-related genes were also prone to miR-138 regulation including APP and BACE1. This study suggests that increased gene dosage of MIR138-2 could contribute to risk for EOAD by regulating different biological pathways implicated in amyloid and tau metabolism. Additional studies are now required to better understand the role of miR-CNVs in EOAD