Genetics of ischaemic stroke in young adults

Terni, E; Giannini, Nicola; Brondi, Marco; Montano, Vincenzo; Bonuccelli, Ubaldo; Mancuso, Michelangelo

doi:10.1016/j.bbacli.2014.12.004

Cited by 33 publications

(33 citation statements)

References 145 publications

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“…Such identification of ncRNAs from WES could be attributed to the sequencing chemistry or impact of library targeted on intergenic regions, which needs a careful reassessment. With a genetic basis for many Mendelian traits/rare diseases not being clear, there are challenges widely seen towards understanding the emergence of mutations for various phenotypes, viz.penetrance [ 13 ], dominance, age-of-onset [ 14 ] and expressivity [ 15 ], complex genetic and environmental interaction studies, etc. [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

Gupta

Tiwari

et al. 2018

Biomolecules

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Congenital Pouch Colon (CPC) is a rare anorectal anomaly common to northwestern India, specifically Rajasthan. Despite efforts to understand the clinical genetic makeup of CPC, no attempt on identifying non-coding RNAs was done. We have earlier reported CPC’s rare variants from whole exome sequencing (WES) across 18 affected samples in a total of 64 subjects. A Smith–Waterman algorithm was used to infer a couple of lncRNAs from WES samples of CPC with predictions from the Noncode database. Further screening and quantification using polymerase chain reaction (PCR), we ascertained interactions using Micro Scale Thermophoresis (MST). We report the role of lnc-EPB41-1-1 shown to be promiscuously interacting with KIF13A substantiating their role in regulation.

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Section: Introductionmentioning

confidence: 99%

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

Gupta

Tiwari

et al. 2018

Biomolecules

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“…Mutations in CACNA1A are known to cause familial hemiplegic migraine type 1 (FHM1) and episodic ataxia type 2 (EA2). The clinical signs of FHM1 overlap significantly with CADASIL, with migraine reported in~20-35% of CADASIL patients and some motor effects may resemble stroke effects [45,46]. Due to a lack of prior clinical information, we cannot exclude other aetiologies for the ischaemic events, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Due to a lack of prior clinical information, we cannot exclude other aetiologies for the ischaemic events, e.g. if they are due to environmental or lifestyle stresses, vasoconstrictive drugs used as a prior treatment or if another gene mutation not tested is the cause [45,47,48]. Another heterozygous gene mutation was identified in ATP1A2 in CAD-400 that is known to cause familial hemiplegic migraine type 2 (FHM2) (MIM#602481).…”

Section: Discussionmentioning

confidence: 99%

Investigating diagnostic sequencing techniques for CADASIL diagnosis

et al. 2020

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations in the NOTCH3 gene. Our laboratory has been undertaking genetic diagnostic testing for CADASIL since 1997. Work originally utilised Sanger sequencing methods targeting specific NOTCH3 exons. More recently, next-generation sequencing (NGS)-based technologies such as a targeted gene panel and whole exome sequencing (WES) have been used for improved genetic diagnostic testing. In this study, data from 680 patient samples was analysed for 764 tests utilising 3 different sequencing technologies. Sanger sequencing was performed for 407 tests, a targeted NGS gene panel which includes NOTCH3 exonic regions accounted for 354 tests, and WES with targeted analysis was performed for 3 tests. In total, 14.7% of patient samples (n = 100/680) were determined to have a mutation. Testing efficacy varied by method, with 10.8% (n = 44/407) of tests using Sanger sequencing able to identify mutations, with 15.8% (n = 56/354) of tests performed using the NGS custom panel successfully identifying mutations and a likely non-NOTCH3 pathogenic variant (n = 1/3) identified through WES. Further analysis was then performed through stratification of the number of mutations detected at our facility based on the number of exons, level of pathogenicity and the classification of mutations as known or novel. A systematic review of NOTCH3 mutation testing data from 1997 to 2017 determined the diagnostic rate of pathogenic findings and found the NGS-customised panel increases our ability to identify disease-causing mutations in NOTCH3.

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“…Ischemic stroke is a heterogeneous multicausal disorder, and epidemiological data have provided substantial evidence for a genetic component of the disease . Hypercoagulability has a more pronounced effect on the risk of ischemic stroke than the risk of myocardial infarction .…”

Section: Introductionmentioning

confidence: 99%

Effect of prothrombotic genotypes on the risk of venous thromboembolism in patients with and without ischemic stroke. The Tromsø Study

Rinde

Morelli

Småbrekke

et al. 2019

Journal of Thrombosis and Haemostasis

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Prothrombotic genotypes may agument the risk of venous thromboembolism (VTE) after ischemic stroke. We studied this effect in a case‐cohort study using a genetic risk score. In stroke patients, a one‐category increase in the genetic risk score was associated with a 50% higher relative risk of VTE. The risk of VTE in stroke patients increased with an increasing number of risk alleles. Summary BackgroundPatients with ischemic stroke have a transiently increased risk of subsequent venous thromboembolism (VTE). Prothrombotic genotypes may augment VTE risk under conditions of high thrombosis risk related to stroke. AimsTo investigate the effect of prothrombotic genotypes in patients with ischemic stroke on the risk of VTE in a population‐based case–cohort study. MethodsCases with incident VTE (n = 664) and a randomly selected age‐weighted subcohort (n = 1817) were sampled from three surveys of the Tromsø Study (1994–2008). Participants were genotyped for ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865) and F11 (rs2036914) single‐nucleotide polymorphisms (SNPs). Cox regression models were used to calculate hazard ratios (HRs) for incident VTE according to individual SNPs and categories of risk alleles (5‐SNP score; 0–1, 2, 3–4 and ≥ 5) in participants with and without ischemic stroke. ResultsThere were 192 patients with incident stroke, of whom 43 developed VTE during a median of 15.2 years of follow‐up. The risk alleles of individual SNPs augmented the elevated VTE risk brought about by ischemic stroke. In stroke patients, a one‐category increase in the genetic risk score was associated with a 50% higher relative risk of overall VTE (HR 1.5, 95% confidence interval [CI] 1.3–1.8) and an 80% higher relative risk of provoked VTE (HR 1.8, 95% CI 1.5–2.1). Stroke patients with ≥ 5 risk alleles had a 12‐fold (HR 11.7, 95% CI 4.1–33.3) higher relative risk of VTE than stroke‐free participants with 0–1 risk alleles. ConclusionsProthrombotic genotypes increased the risk of VTE in stroke patients, and the risk increased with an increasing number of risk alleles.

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Genetics of ischaemic stroke in young adults

Cited by 33 publications

References 145 publications

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

Investigating diagnostic sequencing techniques for CADASIL diagnosis

Effect of prothrombotic genotypes on the risk of venous thromboembolism in patients with and without ischemic stroke. The Tromsø Study

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