14 research outputs found

    Deletion at ITPR1 Underlies Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans

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    We observed a severe autosomal recessive movement disorder in mice used within our laboratory. We pursued a series of experiments to define the genetic lesion underlying this disorder and to identify a cognate disease in humans with mutation at the same locus. Through linkage and sequence analysis we show here that this disorder is caused by a homozygous in-frame 18-bp deletion in Itpr1 (Itpr1Δ18/Δ18), encoding inositol 1,4,5-triphosphate receptor 1. A previously reported spontaneous Itpr1 mutation in mice causes a phenotype identical to that observed here. In both models in-frame deletion within Itpr1 leads to a decrease in the normally high level of Itpr1 expression in cerebellar Purkinje cells. Spinocerebellar ataxia 15 (SCA15), a human autosomal dominant disorder, maps to the genomic region containing ITPR1; however, to date no causal mutations had been identified. Because ataxia is a prominent feature in Itpr1 mutant mice, we performed a series of experiments to test the hypothesis that mutation at ITPR1 may be the cause of SCA15. We show here that heterozygous deletion of the 5′ part of the ITPR1 gene, encompassing exons 1–10, 1–40, and 1–44 in three studied families, underlies SCA15 in humans

    The role of Intravascular Ultrasound in the management of spontaneous coronary artery dissection

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    Abstract Primary or spontaneous coronary artery dissection (SCAD) is an unusual but increasingly recognized cause of acute myocardial ischemia and sudden cardiac death. Typically, SCAD presents in younger patients without conventional risk factors for coronary artery disease. It occurs more commonly in women than in men, and frequently during pregnancy or the postpartum period. Its pathophysiology is poorly understood, and there is considerable controversy regarding the optimal management of patients with SCAD-related myocardial ischemia. Therapeutic approaches include conservative medical therapy, coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). We present four cases of SCAD to illustrate specific aspects of the presentation and management of this condition, with particular reference to the importance of intravascular ultrasound (IVUS) to aid diagnosis and guide subsequent PCI.</p

    Journal of Cardiovascular Magnetic Resonance

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    2012 Non-invasive assessment of coronary artery disease: a comparison of adenosine stress, studied with contrast echocardiography and 3 Tesla cardiovascular magnetic resonanc
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