To determine the importance of GLA mutations in the general stroke population, the frequency of GLA mutations in Japanese male ischaemic stroke (IS) patients with various risk factors and ages was measured.
Twelve patients had missense GLA mutations: 9 with ischemic stroke (p.R118C: n=4; p.D313Y: n=5), including 5 patients with an identified cause of stroke (cardiac embolism: n=2; small vessel disease: n=2; other cause: n=1), 2 with intracerebral hemorrhage (p.R118C: n=1; p.D313Y: n=1), and one with cerebral venous thrombosis (p.R118C: n=1).
Mutations in NOTCH3 causes cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebrovascular disease that leads to ischemic strokes and dementia, but in which migraine is often present, sometimes long before the onset of other symptoms.
We examined the prevalence of factor V Leiden, the prothrombin G20210A genotype, and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in 100 patients (51 males and 49 females) who survived an ischemic stroke without a cardiac embolic source at an age < or = 45 years, and in 238 healthy control subjects from the same geographic area.
To address this issue, we examined the association between prothrombinG20210A and ischemic stroke in a white case-control population and additionally performed a meta-analysis.
Increased Lp (a) levels, the FV G1691A mutation, protein C deficiency, the prothrombinG20210A variant, and the MTHFR TT677 are important risk factors for spontaneous ischemic stroke in childhood.
Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia.
However, rs4929984 is significantly associated with the diastolic blood pressure level of IS patients (additive model: P<sub>adj</sub> = 0.007; dominant model: P<sub>adj</sub> = 0.013), whereas rs217727 is associated with international normalized ratio (additive model: P<sub>adj</sub> = 0.019; recessive model: P<sub>adj</sub> = 0.004), prothrombin time activity level (additive model: P<sub>adj</sub> = 0.026; recessive model: P<sub>adj</sub> = 0.004), and homocysteine level (recessive model: P<sub>adj</sub> = 0.048) in patients with IS.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 mutation-induced vascular smooth muscle cell (VSMC) degeneration, leading to ischemic stroke and vascular dementia.
Correlation with Platelet Parameters and Genetic Markers of Thrombophilia Panel (Factor II g.20210G>A, Factor V Leiden, MTHFR (C677T, A1298C), PAI-1, β-Fibrinogen, Factor XIIIA (V34L), Glycoprotein IIIa (L33P)) in Ischemic Strokes.
We reviewed the currently available data on the relationship between various inherited and acquired coagulation abnormalities (factor V Leiden and prothrombinG20210A mutations, deficiencies of protein C, protein S and anti-thrombin, hyperhomocysteinemia, the antiphospholipid syndrome and increased levels of fibrinogen) and ischemic stroke.
In conclusion, our results indicate that FV Leiden mutation, prothrombinG20210A genotype, and homozygosity for the C677T mutation in the MTHFR gene are not associated with an increased risk for ischemic stroke in young adults.
Some inherited prothrombotic conditions (e.g., Factor V Leiden, G20210Aprothrombin or methylenetetrahydrofolate reductase C677T polymorphism) could also greatly increase the IS risk if present in OC users.
The recently described G20210-->A transition in the 3'-untranslated region of the prothrombin gene is an inherited risk factor for CVT but obviously not for acute ischemic stroke or TIA.
In contrast, prothrombin-20210-mutations were different playing a significant role in the pathogenesis of cerebral sinus vein thrombosis, but not in arterial ischemic stroke.
We describe an unusual case of longitudinal myelitis and ischemic stroke in the presence of homozygous prothrombinG20210A, heterozygous MTHFR 677T mutations and the absence of antiphospholipid antibodies in a young woman with SLE.
Matched case-control study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years.
The risk of ischemic stroke in oral contraceptive users was 13 times higher in women who were also carriers of factor V Leiden and 9 times higher in those who also had hyperhomocysteinemia.
While FV G1691A and prothrombin G20210 A mutations show no significant data in our study, lipoprotein (a) levels >30 mg/dl protein C deficiency, anticardiolipin antibodies and combined prothrombotic disorders seem to be important risk factors for manifestation of ischaemic strokes in children with underlying cardiac disorders.