scholarly journals Whole-exome sequencing in evaluation of patients with venous thromboembolism

2017 ◽  
Vol 1 (16) ◽  
pp. 1224-1237 ◽  
Author(s):  
Eun-Ju Lee ◽  
Daniel J. Dykas ◽  
Andrew D. Leavitt ◽  
Rodney M. Camire ◽  
Eduard Ebberink ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Key Points

Key Points Using WES, we designed an extended thrombophilia panel consisting of 55 genes of significance to thrombosis. The extended thrombophilia panel identified multiple novel genetic variants with predicted roles in thrombosis or thrombophilia.

scholarly journals Whole Exome Sequencing Identifies genetic variants in Chinese Han pregnant women with Venous thromboembolism-a case control study

2020 ◽  
Author(s):  
Yupei Shen ◽  
Yan Zhang ◽  
Ying Xiong ◽  
Zhiping Zhang ◽  
Baohua Zhang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Pregnant Women ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Large Scale ◽  
Single Nucleotide Variants ◽  
Chinese Han ◽  
Whole Exome ◽  
Increased Risk

Abstract Background: Venous thromboembolism (VTE) is a common health problem, causing considerable morbidity and mortality. The incidence of VTE is higher in pregnant women than in those who are not pregnant. However, genetic factors for VTE in pregnant women are largely unknown.Methods: We performed a large-scale prospective cohort study of 65138 pregnancies. Pregnant patients with VTE and pregnant women without VTE were enrolled in the study and sequenced by whole exome sequencing. Functional and enrichment analyses were performed using the DAVID online database. The protein-protein interaction network was constructed using the STRING database. Results: 5810 significant variants were associated with pregnant patients with VTE, including 4874 single nucleotide variants and 936 short deletions which were annotated in 3417 genes (P < 0.05). Fifty-six variants annotated in 46 genes (P < 0.001) and the top 3 variants, including rs2706258 (RNA LOC102724050, p = 1.25 × 10-6), rs17057520 (SCARA3, p = 4.64 × 10-5), and rs3739550 (CAAP1, p = 4.64 × 10-5), were identified. Fourteen low frequency variants had a minor allele frequency (MAF) of less than 1%. Logistic analysis revealed that rs7099478 (GRK5), rs8041208 (WDR72), rs17215792 (KLF7), rs13035688 (KLF7), rs6725221 (KLF7), and rs3214417 (KLF7) were associated with an increased risk of developing VTE (P < 0.05, OR > 1). In addition, combined pathway and PPI analyses revealed that CDC7 and MCM6 involved with DNA replication were associated with VTE in pregnant individuals.Conclusion: The study identified a series of variants and genes that may contribute to VTE in the Chinese pregnant population. Several genes may be risk factors for VTE including KLF7, GRK5, and WDR72. CDC7 and MCM6 may be related to the potential functions of VTE in pregnant women. Notably, the KLF7 gene had 4 genetic variants that were found to be associated with lipid metabolism and cardiovascular diseases. Therefore, further validation is required to reveal the KLF7 mechanism in pregnant women with VTE.

scholarly journals Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

2021 ◽  
Vol 2 (1) ◽  
pp. 100383
Author(s):  
Nicholas S. Diab ◽  
Spencer King ◽  
Weilai Dong ◽  
Garrett Allington ◽  
Amar Sheth ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
De Novo ◽  
Whole Exome ◽  
Analysis Workflow

scholarly journals Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
E Sanchez ◽  
S Grandemange ◽  
F Tran Mau-Them ◽  
P Louis-Plence ◽  
A Carbasse ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

Somatic activating ARAF mutations in Langerhans cell histiocytosis

Blood ◽  
2014 ◽  
Vol 123 (20) ◽  
pp. 3152-3155 ◽  
Author(s):  
David S. Nelson ◽  
Willemijn Quispel ◽  
Gayane Badalian-Very ◽  
Astrid G. S. van Halteren ◽  
Cor van den Bos ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Novel Mutations ◽  
Whole Exome ◽  
Key Points ◽  
Inhibitor Treatment

Key Points Whole exome sequencing reveals novel mutations in ARAF that activate the kinase and are inhibitable by vemurafenib in a patient with LCH. Requiring the presence of BRAF V600E in LCH to qualify for rat fibrosarcoma inhibitor treatment may be overly exclusionary.

scholarly journals A novel mutation in the F5 gene (factor V Amsterdam) associated with bleeding independent of factor V procoagulant function

Blood ◽  
2015 ◽  
Vol 125 (11) ◽  
pp. 1822-1825 ◽  
Author(s):  
Marisa L. R. Cunha ◽  
Kamran Bakhtiari ◽  
Jorge Peter ◽  
J. Arnoud Marquart ◽  
Joost C. M. Meijers ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Bleeding Disorder ◽  
Factor V ◽  
East Texas ◽  
Gain Of Function ◽  
Whole Exome ◽  
Key Points

Key Points A novel gain-of-function mutation in factor V leading to increased levels of TFPI and bleeding was identified by whole exome sequencing. Factor V Amsterdam (F5 C2588G) resembles the mutation (F5 A2350G) leading to East Texas bleeding disorder.

scholarly journals Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations

Blood ◽  
2016 ◽  
Vol 127 (8) ◽  
pp. 1007-1016 ◽  
Author(s):  
Viktor Ljungström ◽  
Diego Cortese ◽  
Emma Young ◽  
Tatjana Pandzic ◽  
Larry Mansouri ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Poor Prognosis ◽  
Clinical Impact ◽  
Lymphocytic Leukemia ◽  
Whole Exome ◽  
Key Points ◽  
Frequent Mutations

Key Points Whole-exome sequencing of CLL patients who relapsed after FCR treatment revealed frequent mutations in RPS15. RPS15 mutations are likely to be early clonal events and confer poor prognosis.

scholarly journals Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Haematologica ◽  
2016 ◽  
Vol 101 (10) ◽  
pp. 1170-1179 ◽  
Author(s):  
B. Johnson ◽  
G. C. Lowe ◽  
J. Futterer ◽  
M. Lordkipanidze ◽  
D. MacDonald ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Inherited Thrombocytopenia

scholarly journals Comprehensive genetic analysis by whole exome sequencing in 352 Korean pediatric patients with unknown neurodevelopmental disorders

2018 ◽  
Author(s):  
Youngha Lee ◽  
Jin Sook Lee ◽  
Soo Yeon Kim ◽  
Jaeso Cho ◽  
Yongjin Yoo ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Neurodevelopmental Disorders ◽  
Pediatric Patients ◽  
Medical System ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variants

AbstractImportanceAccurate diagnosis of pediatric patients with complicated neurological problems demands a well-coordinated combination of robust genetic analytic capability and delicate clinical evaluation. It should be tested whether this challenge can be augmented by whole exome sequencing (WES).ObjectiveTo evaluate the utility of WES-based diagnosis and discovery of novel variants of undiagnosed patients with complex neurodevelopmental problems in a country with a centralized medical system.Design, setting, and participantsA cohort of 352 Korean patients, believed to cover a major portion of the entire country from July 2014 to April 2017, with a broad spectrum of neurodevelopmental disorders without any pathogenic variants revealed by conventional methods were evaluated by trio-based WES at Seoul National University Children’s Hospital.ExposuresWES of patients and parents and subsequent evaluation of genetic variants.Main outcomes and measuresGenetic variants from each patient were evaluated for known disease association and novel variants were assessed for possible involvement with neurodevelopment process.ResultsWe identified disease-causing variants, including newly discovered variants, in 57.4% of the probands, who had underwent a mean of 5.6 years of undiagnosed periods and visited mean of 2.3 tertiary hospitals. The cohort included 112 patients with variants that were previously reported as pathogenic (31.8%), 16 patients with copy number variants (4.5%) and 27 patients with variants that were associated with different clinical symptoms (7.7%). We also discovered potentially pathogenic variants from 47 patients that required further functional assessments (13.4%) and demonstrated potential implications in neurodevelopmental disorders. Following the genetic analysis, we provided more precise treatments to selected patients. A few clinical vignettes are presented that illuminate the potential diagnostic pitfalls that one could have encountered without this approach.Conclusions and relevanceOur results highlight the utility of WES-based diagnosis for improved patient care in a country with a centralized medical system and discovery of novel pathophysiology mechanisms.Key pointsQuestionWhat is the advantage of whole exome sequencing based diagnosis of pediatric neurology patients with unknown rare symptoms in a large tertiary clinic in a country with a centralized medical system?FindingsWhole exome sequencing of 352 Korean patients, with a mean of 5.7 years of undiagnosed period, yielded 44.0% of conservative diagnostic yield. A number of cases were directly benefitted by trio-based WES via termination of diagnostic odyssey, genetic counseling for next offspring, or suggestion of more effective and customized treatment options.MeaningWe report on the establishment of a national-level whole exome-based diagnosis system, with emphasis on deliberate integration of clinical interpretation and genetic analysis. Whole exome sequencing should be a choice of diagnostic tools for pediatric neurologic patients with ambiguous symptoms.

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