Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India.
Results: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood.
Conclusion: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088154 | PMC |
| http://dx.doi.org/10.1186/s40246-024-00613-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Patients who have been treated in intensive care units (ICUs) display a multitude of physical, cognitive, and/or mental impairments that are collectively called post-intensive care syndrome (PICS). People with PICS have difficulty returning to everyday life.
Methods: In this narrative review, we present epidemiologic data, risk factors, and approaches to the prevention and treatment of PICS, along with the evidence supporting them.
What is the preferred mesh placement in primary ventral hernia repair? An international survey of 442 surgeons.
Hernia
September 2025
Center for Perioperative Optimization, Department of Surgery, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 1, Herlev, DK-2730, Denmark.
Purpose: Primary ventral hernia repair is a common elective procedure; however, mesh placement practices vary widely, and there is limited evidence to guide optimal placement. This international study examined surgeons' preferences and considerations regarding mesh placement in elective primary ventral hernia repair.
Methods: We conducted an international cross-sectional survey targeting surgeons experienced in primary ventral hernia repair.
[Validation and clinical value of prognostic model for assessing the risk of severe acute pancreatitis based on inflammatory and hemostasis markers].
Khirurgiia (Mosk)
September 2025
Kuban State Medical University, Krasnodar, Russia.
Objective: To validate and assess clinical efficacy of a prognostic model for predicting severe acute pancreatitis (SAP) based on inflammatory markers (IL-6, ΔIL-22), thromboelastography parameters (K-time) and the BISAP score.
Material And Methods: A prospective observational cohort study enrolled 181 patients with acute pancreatitis. Serum IL-6 and IL-22 were measured in 24 and 48 hours after clinical manifestation, respectively.
Calibration of a gated neutron time-of-flight spectrometer with low-afterglow.
Rev Sci Instrum
September 2025
Key Laboratory for Laser Plasmas (MoE) and School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, China.
Neutron Time-of-Flight (nTOF) detectors are key diagnostics to detect thermonuclear neutrons in laser-fusion experiments. This diagnostic, however, is often plagued by strong gamma-ray noise prior to neutron signals, especially in harsh fast-ignition (FI) environments. To address this issue, a combination of low-afterglow liquid scintillators with time-gated photomultiplier tubes as necessary nTOF components would be a natural solution.
View Article and Find Full Text PDFCD4 T Cells Acquire Innate Capability Upon Classical T Cell Activation.
Eur J Immunol
September 2025
Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Memory T cells, a sizable compartment of the mature immune system, enable enhanced responses upon re-infection with the same pathogen. We have recently shown that virus-experienced innate acting T (T) cells can modulate infectious or autoimmune diseases through TCR-independent IFN-γ production. However, how these cells arise remains unclear.
View Article and Find Full Text PDF