With increasing use of Xpert MTB/RIF a point of care molecular test for simultaneous detection of TB and resistance to rifampicin, a growing number of rifampicin resistant cases are being detected and notified. Insights into the variation and frequencies in the probe mutations obtained through Xpert testing in the RRTB case will form the baseline information for further investigation on drug resistance. In this study we did a retrospective analysis of the GeneXpert data obtained from patient samples received at a National reference laboratory in Chennai between the years 2014 and 2020 to look at the probe distribution, the variation in the mutation and explore its significance. Probe E mutation was most commonly identified followed by Probe D, Probe A, Probe B and Probe C. Coexistence of multiple probe mutations in low bacillary load samples could be related to prolonged amplification cycle leading to delayed hybridization of probes. In such instances reporting false RR in xpert testing is possible. The probe mutations of RR should be monitored in depth with inclusion of codon specific targets for management of drug sensitive TB. In addition, heteroresistance needs to be further tested by alternative genotypic methods to avoid false resistance.
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http://dx.doi.org/10.1016/j.tube.2022.102182 | DOI Listing |
Anal Chem
January 2025
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, Sichuan, China.
Isothermal nucleic acid amplification techniques are promising alternatives to polymerase chain reaction (PCR) for amplifying and detecting nucleic acids under resource-limited conditions. While many isothermal amplification strategies, such as recombinase polymerase amplification (RPA), offer comparable sensitivity to PCR, they often lack the specificity and robustness for discriminating single nucleotide variants (SNVs), mainly due to the uncontrolled production of massive amplicons. Herein, we introduce a mismatch-guided DNA assembly (MGDA) approach capable of discriminating SNVs in the presence of high concentrations of wild-type (WT) interferences.
View Article and Find Full Text PDFOrphanet J Rare Dis
January 2025
The Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Jianshe Rd, Erqi District, Zhengzhou, 450052, Henan, China.
Objective: Spinal muscular atrophy (SMA) is a motor neuron disorder encompassing 5q and non-5q forms, causing muscle weakness and atrophy due to spinal cord cell degeneration. Understanding its genetic basis is crucial for genetic counseling and personalized treatment options.
Methods: This study retrospectively analyzed families of patients suspected of SMA at our institution from February 2006 to March 2024.
Br J Pharmacol
January 2025
Department of Physiology and Pharmacology, School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Background And Purpose: The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ protein, likely through the inhibition of G-protein gated K (GIRK) channels. Here, we investigated the mechanism of ETX inhibition (block) of different GIRKs.
Experimental Approach: We studied ETX inhibition of GIRK channels expressed in Xenopus oocytes with or without their physiological activator, the G protein subunit dimer Gβγ.
Eur Biophys J
January 2025
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Compared to fluorescence, second harmonic generation (SHG) has recently emerged as an excellent signal for imaging probes due to its unmatched advantages in terms of no photobleaching, no phototoxicity, no signal saturation, as well as the superior imaging accuracy with excellent avoidance of background noise. Existing SHG probes are constructed from heavy metals and are cellular exogenous, presenting with high cytotoxicity, difficult cellular uptake, and the limitation of non-heritability. We, therefore, initially propose an innovative gene-encoded bioprotein SHG probe derived from Autographa californica nuclear polyhedrosis virus (AcMNPV) polyhedrin.
View Article and Find Full Text PDFClin Genet
January 2025
Human Molecular Genetics Group, National Health Commission (NHC), Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, China.
The pathogenicity of cholestatic liver diseases (CLDs) remains insufficiently characterized, hindering definitive diagnosis and timely treatment. The aim of this study was to improve the pathogenicity prediction of novel bile acid (BA) transporter variants in patients with CLDs. We analyzed the clinical characteristics and genetic profiles of a CLD cohort (n = 57) using multiple in silico tools and in vitro functional assays.
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