Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients

Owaidah, Tarek; Saleh, Mahasen; Baz, Batoul; Abdulaziz, Basma Al; Al-Zahrani, Hazza; Tarawah, Ahmed; Al-Musa, Abdulrahman; Alnounou, Randa; AbaAlkhail, Hala; Al‐Numair, Nouf S.; Altahan, Rahaf; Abouelhoda, Mohammed; Alamoudi, Thamer; Monies, Dorota; Jabaan, Amjad; Tassan, Nada Al

doi:10.1038/s41525-019-0079-6

Cited by 12 publications

(21 citation statements)

References 36 publications

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“…A total of 35,144 patients with AAA and 2,572,386 controls were investigated independently in 16 studies [20] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] . Many studies had overlapping cohorts by using the same datasets to conduct analyses on their respective causal risk factors, with the most common overlaps occurring with the UK biobank (9 studies) [23] , [27] , [28] , [29] , [31] , [34] , [36] , [37] , [38] and the Utrecht Netherlands dataset (4 studies) [20] , [25] , [32] , [33] . Further details regarding datasets are provided in supplement table 3.…”

Section: Resultsmentioning

confidence: 99%

“…The number of cases and controls across studies ranged between 155 and 7642 and 155 to 366,549 respectively. The studies included participants recruited from multiple datasets in countries including Australia [20] , [24] , [25] , [32] , UK [20] , [23] , [24] , [25] , [27] , [28] , [29] , [31] , [32] , [34] , [36] , [37] , New Zealand [20] , [25] , [32] , Iceland [20] , [32] , The Netherlands [20] , [25] , [32] , [33] , Scotland [25] , China [30] and the USA [20] , [32] , [35] . Further details are presented in supplementary table 1 .…”

Section: Resultsmentioning

confidence: 99%

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Systematic review and Meta-Analysis of Mendelian randomisation analyses of Abdominal aortic aneurysms

Ibrahim

Thanigaimani

Singh

et al. 2021

IJC Heart & Vasculature

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Introduction Mendelian randomisation (MR) has been suggested to be able to overcome biases of observational studies, but no meta-analysis is available on MR studies on abdominal aortic aneurysm (AAA). This systematic review and Meta-analysis examined the evidence of causal risk factors for AAA identified in MR studies. Methods Publicly available databases were systematically searched for MR studies that reported any causal risk factors for AAA diagnosis. Meta-analyses were performed using random effect models and reported as odds ratio (OR) and 95% confidence intervals (CI). Study quality was assessed using a modified version of Strengthening the Reporting of Mendelian Randomisation Studies (STROBE-MR) guidelines. Results Sixteen MR studies involving 34,050 patients with AAA and 2,205,894 controls were included. Meta-analyses suggested that one standard deviation increase in high density lipoprotein (HDL) significantly reduced (OR: 0.66, 95% CI: 0.61, 0.72) and one standard deviation increase in low density lipoprotein (LDL) significantly increased the risk (OR: 1.68, 95%, CI: 1.55, 1.82) of AAA. One standard deviation increase in triglycerides did not significantly increase the risk of AAA (OR: 1.21, 95% CI: 0.86, 1.71). Quality assessment suggested that ten and five studies were of low and moderate risk of bias respectively, with one study considered as high risk of bias. Conclusion This meta-analysis suggests LDL and HDL are positive and negative casual risk factors for AAA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Systematic review and Meta-Analysis of Mendelian randomisation analyses of Abdominal aortic aneurysms

Ibrahim

Thanigaimani

Singh

et al. 2021

IJC Heart & Vasculature

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“…We have selected the genes based on their prevalence globally and in the Saudi population [39][40][41][42] . Genes associated with Glanzmann Thrombasthenia, a rare genetic bleeding disorder, were excluded since they were evaluated in an earlier study 20 , whereby 72 individuals were screened and 17 mutations were identified in ITGA2B and ITGB3.…”

Section: Selection Of Genesmentioning

confidence: 99%

“…In blood and bleeding disorders, examples of targeted gene panels are the SHGP heme 20 and the ThromboGenomics consortium panels 21 . In the current study, we analyzed the data from the SHGP to redefine and classify both pathogenic and benign variants in 17 selected genes that are associated with different blood and bleeding disorders.…”

Section: Introductionmentioning

confidence: 99%

Molecular classification of blood and bleeding disorder genes

et al. 2021

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The advances and development of sequencing techniques and data analysis resulted in a pool of informative genetic data, that can be analyzed for informing decision making in designing national screening, prevention programs, and molecular diagnostic tests. The accumulation of molecular data from different populations widen the scope of utilization of this information. Bleeding disorders are a heterogeneous group of clinically overlapping disorders. We analyzed the targeted sequencing data from ~1285 Saudi individuals in 17 blood and bleeding disorders genes, to determine the frequency of mutations and variants. We used a replication set of ~5000 local exomes to validate pathogenicity and determine allele frequencies. We identified a total of 821 variants, of these 98 were listed in HGMD as disease related variants and 140 were novel variants. The majority of variants were present in VWF, followed by F5, F8, and G6PD genes, while FGG, FGB, and HBA1 had the lowest number of variants. Our analysis generated a priority list of genes, mutations and novel variants. This data will have an impact on informing decisions for screening and prevention programs and in management of vulnerable patients admitted to emergency, surgery, or interventions with bleeding side effects.

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“…84,85 Genetic sequencing of ITGA2B and ITGB3 may also be performed to confirm the specific mutations involved. Multiple groups [86][87][88][89] have recently developed high-throughput molecular diagnostic assays for patients with GT and other inherited bleeding disorders. It should be noted though that at this time, there does not seem to be a correlation between specific mutation and phenotype severity 8 and even family members sharing similar mutations have been shown to have significant variability amongst their clinical outcomes.…”

Section: Diagnosismentioning

confidence: 99%

Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies

Mathews¹,

Rivard²,

Bonnefoy³

2021

JBM

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Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder of fibrinogen-mediated platelet aggregation due to a quantitative or qualitative deficit of the α IIb β 3 integrin at the platelet surface membrane resulting from mutation(s) in ITGA2B and/or ITGB3 . Patients tend to present in early childhood with easy bruising and mucocutaneous bleeding. The diagnostic process requires consideration of more common disorders of haemostasis and coagulation prior to confirming the disorder with platelet light transmission aggregation, flow cytometry of CD41 and CD61 expression, and/or exon sequencing of ITGA2B and ITGB3 . Antifibrinolytic therapy, recombinant activated factor VII, and platelet transfusions are the mainstay of therapy, although the latter may trigger formation of anti-platelet antibodies in GT patients and inadvertent platelet-refractory disease. The management of these patients therefore remains complex, particularly in the context of trauma, labour and delivery, and perioperative care. Bone marrow transplantation remains the sole curative option, although the venue of gene therapy is being increasingly explored as a future alternative for definitive treatment of GT.

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Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients

Cited by 12 publications

References 36 publications

Systematic review and Meta-Analysis of Mendelian randomisation analyses of Abdominal aortic aneurysms

Systematic review and Meta-Analysis of Mendelian randomisation analyses of Abdominal aortic aneurysms

Molecular classification of blood and bleeding disorder genes

Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies

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