scholarly journals Diagnostic Yield of Next-Generation Sequencing in Patients With Chronic Kidney Disease of Unknown Etiology

2019 ◽  
Vol 10 ◽  
Author(s):  
Amber de Haan ◽  
Mark Eijgelsheim ◽  
Liffert Vogt ◽  
Nine V. A. M. Knoers ◽  
Martin H. de Borst
Keyword(s):  
Chronic Kidney Disease ◽  
Next Generation Sequencing ◽  
Kidney Disease ◽  
Diagnostic Yield ◽  
Unknown Etiology ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Biomarkers and Next Generation Sequencing in Chronic Kidney Disease

2016 ◽  
Vol 2 (1) ◽  
pp. 23-25
Author(s):  
Ying Shi ◽  
◽  
Hao Yi ◽  
Chunling Huang ◽  
Carol A. Pollock ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Next Generation Sequencing ◽  
Kidney Disease ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Next Generation Sequencing in Pediatric Epilepsy Using Customized Panels: Size Matters

2020 ◽  
Author(s):  
Eva-Katharina Willimsky ◽  
Anna Munzig ◽  
Karin Mayer ◽  
Saskia Biskup ◽  
Angela Abicht ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Diagnostic Yield ◽  
Unknown Etiology ◽  
Pediatric Epilepsy ◽  
Next Generation ◽  
Large Panels ◽  
Pathogenic Variants ◽  
Gene Panels ◽  
Patients With Epilepsy ◽  
Generation Sequencing

Abstract Introduction Next generation sequencing (NGS) with customized gene panels is a helpful tool to identify monogenic epilepsy syndromes. The number of genes tested within a customized panel may vary greatly. The aim of the present study was to compare the diagnostic yield of small (<25 kb) and large (>25 kb) customized epilepsy panels. Methods This retrospective cohort study investigated data of 190 patients of 18 years or younger, with the diagnosis of an epilepsy of unknown etiology who underwent NGS using customized gene panels. Small (<25 kb) and large (>25 kb) panels were compared regarding the distribution of benign/likely benign and pathogenic/likely pathogenic variants and variants of unclear significance. In addition, differences of the diagnostic yield with respect to epilepsy severity, i.e., developmental and epileptic encephalopathy [DEE] vs. non-DEE, were analyzed. Results The diagnostic yield defined as pathogenic or likely pathogenic variants in large panels was significantly increased (29% [n = 14/48] vs. 13% [n = 18/142], p = 0.0198) compared with smaller panels. In non-DEE patients the increase of the diagnostic yield in large panels was significant(35% n = 6/17 vs. 13% n = 12/94, p = 0.0378), which was not true for DEE patients. Discussion This study indicates that large panels are superior for pediatric patients with epilepsy forms without encephalopathy (non-DEE). For patients suffering from DEE small panels of a maximum of 10 genes seem to be sufficient. The proportion of unclear findings increases with rising panel sizes. Conclusion Customized epilepsy panels of >25 kb compared with smaller panels show a significant higher diagnostic yield in patients with epilepsy especially in non-DEE patients.

scholarly journals Identification of a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for chronic kidney disease using next-generation sequencing

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052096948
Author(s):  
Xinying Liu ◽  
Weijie Wang ◽  
Yaling Bai ◽  
Huiran Zhang ◽  
Shenglei Zhang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Next Generation Sequencing ◽  
Kidney Disease ◽  
Expression Profile ◽  
Fold Change ◽  
Next Generation ◽  
Qrt Pcr ◽  
Genome Wide ◽  
A Genome ◽  
Generation Sequencing

Objective To identify serum microRNAs (miRNAs) as potential non-invasive biomarkers for patients with chronic kidney disease (CKD). Methods We collected serum samples from healthy controls, CKD stage 1 (CKD1), and stage 5 (CKD5) patients with primary glomerulonephritis (GN), screened differentially expressed miRNAs (DEMs) using next-generation sequencing (NGS), and confirmed the sequencing data using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results We identified 20 and 42 DEMs in the CKD1 and CKD5 patients compared with the controls, respectively, and 70 DEMs in the CKD5 compared with the CKD1 patients. The qRT-PCR results showed that miR-483-5p was up-regulated in the CKD1 and CKD5 patients compared with controls (fold change = 2.56 and 18.77, respectively). miR-363-3p was down-regulated in the CKD5 patients compared with the controls and CKD1 patients (fold change = 0.27 and 0.48, respectively). Conclusion We identified a genome-wide serum miRNA expression profile in CKD patients, and serum miR-483-5p and miR-363-3p may act as potential diagnostic biomarkers for CKD.

scholarly journals Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients

2021 ◽  
Author(s):  
Mohamed Z. Alimohamed ◽  
LennartF. Johansson ◽  
Anna Posafalvi ◽  
Ludolf G. Boven ◽  
Krista K. van Dijk ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Diagnostic Yield ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing

2016 ◽  
Vol 54 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Francisco Martínez ◽  
Alfonso Caro-Llopis ◽  
Mónica Roselló ◽  
Silvestre Oltra ◽  
Sonia Mayo ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Next Generation Sequencing ◽  
Diagnostic Yield ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
High Diagnostic Yield ◽  
Generation Sequencing

scholarly journals No Metagenomic Evidence of Causative Viral Pathogens in Postencephalitic Parkinsonism Following Encephalitis Lethargica

2021 ◽  
Vol 9 (8) ◽  
pp. 1716
Author(s):  
Dániel Cadar ◽  
Kurt A. Jellinger ◽  
Peter Riederer ◽  
Sabrina Strobel ◽  
Camelia-Maria Monoranu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Neuronal Loss ◽  
Unknown Etiology ◽  
Next Generation ◽  
Encephalitis Lethargica ◽  
Tissue Samples ◽  
Viral Pathogen ◽  
Postencephalitic Parkinsonism ◽  
Generation Sequencing ◽  
Post Infectious

Postencephalitic parkinsonism (PEP) is a disease of unknown etiology and pathophysiology following encephalitis lethargica (EL), an acute-onset polioencephalitis of cryptic cause in the 1920s. PEP is a tauopathy with multisystem neuronal loss and gliosis, clinically characterized by bradykinesia, rigidity, rest tremor, and oculogyric crises. Though a viral cause of EL is likely, past polymerase chain reaction-based investigations in the etiology of both PEP and EL were negative. PEP might be caused directly by an unknown viral pathogen or the consequence of a post-infectious immunopathology. The development of metagenomic next-generation sequencing in conjunction with bioinformatic techniques has generated a broad-range tool for the detection of unknown pathogens in the recent past. Retrospective identification and characterization of pathogens responsible for past infectious diseases can be successfully performed with formalin-fixed paraffin-embedded (FFPE) tissue samples. In this study, we analyzed 24 FFPE brain samples from six patients with PEP by unbiased metagenomic next-generation sequencing. Our results show that no evidence for the presence of a specific or putative (novel) viral pathogen was found, suggesting a likely post-infectious immune-mediated etiology of PEP.

scholarly journals Next-Generation Sequencing Gene Panels and “Solo” Clinical Exome Sequencing Applied in Structurally Abnormal Fetuses

2021 ◽  
pp. 1-11
Author(s):  
Montse Pauta ◽  
Berta Campos ◽  
Maria Segura-Puimedon ◽  
Gemma Arca ◽  
Alfons Nadal ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Exome Sequencing ◽  
Diagnostic Yield ◽  
Monogenic Disease ◽  
Chromosomal Microarray Analysis ◽  
Next Generation ◽  
Clinical Exome Sequencing ◽  
Gene Panels ◽  
Generation Sequencing ◽  
Structural Anomalies

<b><i>Objective:</i></b> The aim of the study was to assess the diagnostic yield of 2 different next-generation sequencing (NGS) approaches: gene panel and “solo” clinical exome sequencing (solo-CES), in fetuses with structural anomalies and normal chromosomal microarray analysis (CMA), in the absence of a known familial mutation. <b><i>Methodology:</i></b> Gene panels encompassing from 2 to 140 genes, were applied mainly in persistent nuchal fold/fetal hydrops and in large hyperechogenic kidneys. Solo-CES, which entails sequencing the fetus alone and only interpreting the Online Mendelian Inheritance in Man genes, was performed in multisystem or recurrent structural anomalies. <b><i>Results:</i></b> During the study period (2015–2020), 153 NGS studies were performed in 148 structurally abnormal fetuses with a normal CMA. The overall diagnostic yield accounted for 35% (53/153) of samples and 36% (53/148) of the fetuses. Diagnostic yield with the gene panels was 31% (15/49), similar to 37% (38/104) in solo-CES. <b><i>Conclusions:</i></b> A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES.

scholarly journals Targeted next generation sequencing identifies a genetic spectrum of DNA variants in patients with hemiplegic migraine

2019 ◽  
Vol 2 ◽  
pp. 251581631988163 ◽  
Author(s):  
Neven Maksemous ◽  
Robert A Smith ◽  
Heidi G Sutherland ◽  
Bridget H Maher ◽  
Omar Ibrahim ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Diagnostic Yield ◽  
Next Generation ◽  
Hemiplegic Migraine ◽  
Targeted Next Generation Sequencing ◽  
Variants Of Unknown Significance ◽  
High Mutation Frequency ◽  
Unknown Significance ◽  
Atp1a2 Gene ◽  
Generation Sequencing

Objective: Hemiplegic migraine in both familial (FHM) and sporadic (SHM) forms is a rare subtype of migraine with aura that can be traced to mutations in the CACNA1A, ATP1A2 and SCN1A genes. It is characterised by severe attacks of typical migraine accompanied by hemiparesis, as well as episodes of complex aura that vary significantly between individuals. Methods: Using a targeted next generation sequencing (NGS) multigene panel, we have sequenced the genomic DNA of 172 suspected hemiplegic migraine cases, in whom no mutation had previously been found by Sanger sequencing (SS) of a limited number of exons with high mutation frequency in FHM genes. Results: Genetic screening identified 29 variants, 10 of which were novel, in 35 cases in the three FHM genes ( CACNA1A, ATP1A2 and SCN1A). Interestingly, in this suspected HM cohort, the ATP1A2 gene harboured the highest number of variants with 24/35 cases (68.6%), while CACNA1A ranked the second gene, with 5 variants identified in 7/35 cases (20%). All detected variants were confirmed by SS and were absent in 100 non-migraine healthy control individuals. Assessment of variants with the American College of Medical Genetics and Genomics guidelines classified 8 variants as pathogenic, 3 as likely pathogenic and 18 as variants of unknown significance. Targeted NGS gene panel increased the diagnostic yield by fourfold over iterative SS in our diagnostics facility. Conclusion: We have identified 29 potentially causative variants in an Australian and New Zealand cohort of suspected HM cases and found that the ATP1A2 gene was the most commonly mutated gene. Our results suggest that screening using NGS multigene panels to investigate ATP1A2 alongside CACNA1A and SCN1A is a clinically useful and efficient method.

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