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Chapter 5 - Genetics of stroke

from Part I - General principles

Published online by Cambridge University Press:  05 August 2016

By
Stéphanie Debette  and
Louis R Caplan
Edited by
Louis R. Caplan
Louis R. Caplan
Affiliation:
Department of Neurology, Beth Israel Deaconess Medical Center, Massachusetts
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Caplan's Stroke
A Clinical Approach
 , pp. 129 - 144
Publisher: Cambridge University Press
Print publication year: 2016

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References

Seshadri, S, Wolf, PA. Lifetime risk of stroke and dementia: Current concepts, and estimates from the Framingham Study. Lancet Neurol 2007;6:1106–1114.Google Scholar
Johnston, SC, Mendis, S, Mathers, CD. Global variation in stroke burden and mortality: Estimates from monitoring, surveillance, and modelling. Lancet Neurol 2009;8:345–354.CrossRefGoogle ScholarPubMed
Gorelick, PB, Scuteri, A, Black, SE, et al. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672–2713.Google Scholar
Viswanathan, A, Rocca, WA, Tzourio, C. Vascular risk factors and dementia: How to move forward? Neurology 2009;72:368–374.CrossRefGoogle ScholarPubMed
Pendlebury, ST, Rothwell, PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: A systematic review and meta-analysis. Lancet Neurol 2009;8:1006–1018.CrossRefGoogle ScholarPubMed
Falcone, GJ, Malik, R, Dichgans, M, Rosand, J. Current concepts and clinical applications of stroke genetics. Lancet Neurol 2014;13:405–418.CrossRefGoogle ScholarPubMed
Manolio, TA. Bringing genome-wide association findings into clinical use. Nat Rev Genet 2013;14:549–558.Google Scholar
Leys, D, Bandu, L, Henon, H, et al. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002;59:26–33.Google Scholar
Chabriat, H, Joutel, A, Dichgans, M, Tournier-Lasserve, E, Bousser, M-G. Cadasil. Lancet Neurol 2009;8:643–653.Google Scholar
Joutel, A, Corpechot, C, Ducros, A, et al. Notch 3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383:707–710.Google Scholar
Dichgans, M. Monogenic causes of ischemic stroke. In Stroke Genetics, Markus, H (ed). Oxford: Oxford University Press, 2003.Google Scholar
Razvi, SS, Davidson, R, Bone, I, Muir, KW. The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland. J Neurol Neurosurg Psychiatry 2005;76:739–741.CrossRefGoogle ScholarPubMed
Dong, Y, Hassan, A, Zhang, Z, Huber, D, Dalageorgou, C, Markus, HS. Yield of screening for CADASIL mutations in lacunar stroke and leukoaraiosis. Stroke 2003;34:203–205.Google Scholar
O’Sullivan, M, Jarosz, JM, Martin, RJ, Deasy, N, Powell, JF, Markus, HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 2001;56:628–634.Google Scholar
Chabriat, H, Levy, C, Taillia, H, et al. Patterns of MRI lesions in CADASIL. Neurology 1998;51:452–457.Google Scholar
Gobron, C, Viswanathan, A, Bousser, M-G, Chabriat, H. Multiple simultaneous cerebral infarctions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Cerebrovasc Dis 2006;22:445–446.CrossRefGoogle ScholarPubMed
Yao, M, Herve, D, Jouvent, E, et al. Dilated perivascular spaces in small-vessel disease: A study in CADASIL. Cerebrovasc Dis 2014;37:155–163.Google Scholar
Ruchoux, MM, Chabriat, H, Bousser, M-G, Baudrimont, M, Tournier-Lasserve, E. Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 1994;25:2291–2292.CrossRefGoogle ScholarPubMed
Dichgans, M, Markus, HS, Salloway, S, et al. Donepezil in patients with subcortical vascular cognitive impairment: A randomised double-blind trial in CADASIL. Lancet Neurol 2008;7:310–318.CrossRefGoogle ScholarPubMed
Hara, K, Shiga, A, Fukutake, T, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med 2009;360:1729–1739.CrossRefGoogle ScholarPubMed
Bayrakli, F, Balaban, H, Gurelik, M, Hizmetli, S, Topaktas, S. Mutation in the HTRA1 gene in a patient with degenerated spine as a component of CARASIL syndrome. Turk Neurosurg 2014;24:67–69.Google Scholar
Zheng, DM, Xu, FF, Gao, Y, Zhang, H, Han, SC, Bi, GR. A Chinese pedigree of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): Clinical and radiological features. J Clin Neurosci 2009;16:847–849.CrossRefGoogle ScholarPubMed
Mendioroz, M, Fernandez-Cadenas, I, Del Rio-Espinola, A, et al. A missense HTRA1 mutation expands CARASIL syndrome to the Caucasian population. Neurology 2010;75:2033–2035.CrossRefGoogle Scholar
Yanagawa, S, Ito, N, Arima, K, Ikeda, S. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Neurology 2002;58:817–820.Google Scholar
Bianchi, S, Di Palma, C, Gallus, GN, et al. Two novel HTRA1 mutations in a European CARASIL patient. Neurology 2014;82:898–900.Google Scholar
Nozaki, H, Nishizawa, M, Onodera, O. Features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2014;45:3447–3453.CrossRefGoogle ScholarPubMed
Fukutake, T. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): From discovery to gene identification. J Stroke Cerebrovasc Dis 2011;20:85–93.Google Scholar
Fukutake, T, Hirayama, K. Familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension. Eur Neurol 1995;35:69–79.Google Scholar
Terwindt, GM, Haan, J, Ophoff, RA, et al. Clinical and genetic analysis of a large Dutch family with autosomal dominant vascular retinopathy, migraine and Raynaud’s phenomenon. Brain 1998;121(Pt 2):303–316.Google Scholar
Grand, MG, Kaine, J, Fulling, K, et al. Cerebroretinal vasculopathy. A new hereditary syndrome. Ophthalmology 1988;95:649–659.Google Scholar
Jen, J, Cohen, AH, Yue, Q, et al. Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Neurology 1997;49:1322–1330.Google Scholar
Richards, A, van den Maagdenberg, AM, Jen, JC, et al. C-terminal truncations in human 3‘-5‘ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 2007;39:1068–1070.Google Scholar
Stuart, MJ, Nagel, RL. Sickle-cell disease. Lancet 2004;364:1343–1360.Google Scholar
Howard, J, Davies, SC. Sickle cell disease in North Europe. Scand J Clin Lab Invest 2007;67:27–38.CrossRefGoogle ScholarPubMed
Rees, DC, Williams, TN, Gladwin, MT. Sickle-cell disease. Lancet 2010;376:2018–2031.CrossRefGoogle ScholarPubMed
Ohene-Frempong, K, Weiner, SJ, Sleeper, LA, et al. Cerebrovascular accidents in sickle cell disease: Rates and risk factors. Blood 1998;91:288–294.Google ScholarPubMed
Bernaudin, F, Verlhac, S, Arnaud, C, et al. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood 2011;117:1130–1140.Google Scholar
Switzer, JA, Hess, DC, Nichols, FT, Adams, RJ. Pathophysiology and treatment of stroke in sickle-cell disease: Present and future. Lancet Neurol 2006;5:501–512.Google Scholar
Kossorotoff, M, Brousse, V, Grevent, D, et al. Cerebral haemorrhagic risk in children with sickle-cell disease. Dev Med Child Neurol 2015;57:187–193.CrossRefGoogle ScholarPubMed
Fullerton, HJ, Adams, RJ, Zhao, S, Johnston, SC. Declining stroke rates in Californian children with sickle cell disease. Blood 2004;104:336–339.Google Scholar
Adams, RJ, McKie, VC, Hsu, L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998;339:5–11.Google Scholar
Verduzco, LA, Nathan, DG. Sickle cell disease and stroke. Blood 2009;114:5117–5125.Google Scholar
Gaustadnes, M, Ingerslev, J, Rutiger, N. Prevalence of congenital homocystinuria in Denmark. N Engl J Med 1999;340:1513.Google Scholar
Mudd, SH, Skovby, F, Levy, HL, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985;37:1–31.Google ScholarPubMed
Welch, GN, Loscalzo, J. Homocysteine and atherothrombosis. N Engl J Med 1998;338:1042–1050.Google Scholar
Bellamy, MF, McDowell, IF. Putative mechanisms for vascular damage by homocysteine. J Inherit Metab Dis 1997;20:307–315.Google Scholar
Kelly, PJ, Furie, KL, Kistler, JP, et al. Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency. Neurology 2003;60:275–279.Google Scholar
Germain, DP. Fabry disease. Orphanet J Rare Dis 2010;5:30.Google Scholar
Rolfs, A, Bottcher, T, Zschiesche, M, et al. Prevalence of Fabry disease in patients with cryptogenic stroke: A prospective study. Lancet 2005;366:1794–1796.CrossRefGoogle ScholarPubMed
Sarikaya, H, Yilmaz, M, Michael, N, Miserez, AR, Steinmann, B, Baumgartner, RW. Zurich Fabry study – prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA. Eur J Neurol 2012;19:1421–1426.Google Scholar
Wozniak, MA, Kittner, SJ, Tuhrim, S, et al. Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke. Stroke 2010;41:78–81.Google Scholar
Brouns, R, Sheorajpanday, R, Braxel, E, et al. Middelheim Fabry Study (MiFaS): A retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke. Clin Neurol Neurosurg 2007;109:479–484.Google Scholar
Rolfs, A, Fazekas, F, Grittner, U, et al. Acute cerebrovascular disease in the young: The Stroke in Young Fabry Patients Study. Stroke 2013;44:340–349.CrossRefGoogle Scholar
Sims, K, Politei, J, Banikazemi, M, Lee, P. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: Natural history data from the Fabry Registry. Stroke 2009;40:788–794.Google Scholar
Kolodny, E, Fellgiebel, A, Hilz, MJ, et al. Cerebrovascular involvement in Fabry disease: Current status of knowledge. Stroke 2015;46:302–313.Google Scholar
Nakamura, K, Sekijima, Y, Hattori, K, et al. Cerebral hemorrhage in Fabry’s disease. J Hum Genet 2010;55:259–261.CrossRefGoogle ScholarPubMed
Crutchfield, KE, Patronas, NJ, Dambrosia, JM, et al. Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology 1998;50:1746–1749.CrossRefGoogle ScholarPubMed
Fellgiebel, A, Keller, I, Martus, P, et al. Basilar artery diameter is a potential screening tool for Fabry disease in young stroke patients. Cerebrovasc Dis 2011;31:294–299.CrossRefGoogle ScholarPubMed
Zarate, YA, Hopkin, RJ. Fabry’s disease. Lancet 2008;372:1427–1435.Google Scholar
Schiffmann, R, Kopp, JB, Austin, HA 3rd, et al. Enzyme replacement therapy in Fabry disease: A randomized controlled trial. JAMA 2001;285:2743–2749.CrossRefGoogle ScholarPubMed
Vanakker, OM, Leroy, BP, Coucke, P, et al. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat 2008;29:205.CrossRefGoogle Scholar
Debette, S, Germain, DP. Neurologic manifestations of inherited disorders of connective tissue. Handb Clin Neurol 2014;119:565–576.CrossRefGoogle ScholarPubMed
van den Berg, JS, Hennekam, RC, Cruysberg, JR, et al. Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. Cerebrovasc Dis 2000;10:315–319.Google Scholar
Germain, DP, Boutouyrie, P, Laloux, B, Laurent, S. Arterial remodeling and stiffness in patients with pseudoxanthoma elasticum. Arterioscler Thromb Vasc Biol 2003;23:836–841.CrossRefGoogle ScholarPubMed
Dalloz, MA, Debs, R, Bensa, C, Alamowitch, S. [White matter lesions leading to the diagnosis of pseudoxanthoma elasticum]. Rev Neurol (Paris);166:844–848.CrossRefGoogle Scholar
Renard, D, Castelnovo, G, Jeanjean, L, Perrochia, H, Brunel, H, Labauge, P. Teaching neuroimage: Microangiopathic complications in pseudoxanthoma elasticum. Neurology 2008;71:e69.CrossRefGoogle ScholarPubMed
Pavlovic, AM, Zidverc-Trajkovic, J, Milovic, MM, et al. Cerebral small vessel disease in pseudoxanthoma elasticum: Three cases. Can J Neurol Sci 2005;32:115–118.Google Scholar
Neldner, KH. Pseudoxanthoma elasticum. Clin Dermatol 1988;6:1–159.Google Scholar
De Paepe, A, Viljoen, D, Matton, M, et al. Pseudoxanthoma elasticum: Similar autosomal recessive subtype in Belgian and Afrikaner families. Am J Med Genet 1991;38:16–20.Google Scholar
Uitto, J, Li, Q, Jiang, Q. Pseudoxanthoma elasticum: Molecular genetics and putative pathomechanisms. J Invest Dermatol;130:661–670.CrossRefGoogle Scholar
Germain, DP. Ehlers–Danlos syndrome type IV. Orphanet J Rare Dis 2007;2:32.Google Scholar
Beighton, P, De Paepe, A, Steinmann, B, Tsipouras, P, Wenstrup, RJ. Ehlers–Danlos syndromes: Revised nosology, Villefranche, 1997. Ehlers–Danlos National Foundation (USA) and Ehlers–Danlos Support Group (UK). Am J Med Genet 1998;77:31–37.Google Scholar
Pepin, M, Schwarze, U, Superti-Furga, A, Byers, PH. Clinical and genetic features of Ehlers–Danlos syndrome type IV, the vascular type. N Engl J Med 2000;342:673–680.Google Scholar
North, KN, Whiteman, DA, Pepin, MG, Byers, PH. Cerebrovascular complications in Ehlers–Danlos syndrome type IV. Ann Neurol 1995;38:960–964.CrossRefGoogle ScholarPubMed
Debette, S, Goeggel Simonetti, B, Schilling, S, et al. Familial occurrence and heritable connective tissue disorders in cervical artery dissection. Neurology 2014;83:2023–2031.Google Scholar
Arnold, M, Bousser, M-G, Fahrni, G, et al. Vertebral artery dissection: Presenting findings and predictors of outcome. Stroke 2006;37:2499–2503.Google Scholar
Leys, D, Moulin, T, Stojkovic, T, Begey, S, Chavot, D, DONALD Investigators. Follow-up of patients with history of cervical artery dissection. Cerebrovasc Dis 1995;5:43–49.CrossRefGoogle Scholar
Schievink, WI, Mokri, B, O’Fallon, WM. Recurrent spontaneous cervical-artery dissection. N Engl J Med 1994;330:393–397.Google Scholar
Beletsky, V, Nadareishvili, Z, Lynch, J, Shuaib, A, Woolfenden, A, Norris, JW. Cervical arterial dissection: Time for a therapeutic trial? Stroke 2003;34:2856–2860.Google Scholar
Touze, E, Gauvrit, JY, Moulin, T, Meder, JF, Bracard, S, Mas, JL. Risk of stroke and recurrent dissection after a cervical artery dissection: A multicenter study. Neurology 2003;61:1347–1351.Google Scholar
Arnold, M, Kappeler, L, Georgiadis, D, et al. Gender differences in spontaneous cervical artery dissection. Neurology 2006;67:1050–1052.CrossRefGoogle ScholarPubMed
Debette, S, Leys, D. Cervical-artery dissections: Predisposing factors, diagnosis, and outcome. Lancet Neurol 2009;8:668–678.Google Scholar
Engelter, ST, Brandt, T, Debette, S, et al. Antiplatelets versus anticoagulation in cervical artery dissection. Stroke 2007;38:2605–2611.Google Scholar
Schievink, WI, Limburg, M, Oorthuys, JW, Fleury, P, Pope, FM. Cerebrovascular disease in Ehlers–Danlos syndrome type IV. Stroke 1990;21:626–632.Google Scholar
Ong, KT, Perdu, J, De Backer, J, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers–Danlos syndrome: A prospective randomised, open, blinded-endpoints trial. Lancet 2010;376:1476–1484.Google Scholar
Gray, JR, Bridges, AB, West, RR, et al. Life expectancy in British Marfan syndrome populations. Clin Genet 1998;54:124–128.Google Scholar
Schievink, WI, Michels, VV, Piepgras, DG. Neurovascular manifestations of heritable connective tissue disorders. A review. Stroke 1994;25:889–903.Google Scholar
Wityk, RJ, Zanferrari, C, Oppenheimer, S. Neurovascular complications of Marfan syndrome: A retrospective, hospital-based study. Stroke 2002;33:680–684.Google Scholar
Ho, NC, Tran, JR, Bektas, A. Marfan’s syndrome. Lancet 2005;366:1978–1981.Google Scholar
Lynch, DR, Dawson, TM, Raps, EC, Galetta, SL. Risk factors for the neurologic complications associated with aortic aneurysms. Arch Neurol 1992;49:284–288.Google Scholar
Spittell, PC, Spittell, JA Jr., Joyce, JW, et al. Clinical features and differential diagnosis of aortic dissection: Experience with 236 cases (1980 through 1990). Mayo Clin Proc 1993;68:642–651.Google Scholar
Bonnin, P, Giannesini, C, Amah, G, Kevorkian, JP, Woimant, F, Levy, BI. Doppler sonograpy with dynamic testing in a case of aortic dissection extending to the innominate and right common carotid arteries. Neuroradiology 2003;45:472–475.Google Scholar
Youl, BD, Coutellier, A, Dubois, B, Leger, JM, Bousser, M-G. Three cases of spontaneous extracranial vertebral artery dissection. Stroke 1990;21:618–625.Google Scholar
Schievink, WI, Bjornsson, J, Piepgras, DG. Coexistence of fibromuscular dysplasia and cystic medial necrosis in a patient with Marfan’s syndrome and bilateral carotid artery dissections. Stroke 1994;25:2492–2496.Google Scholar
Harrer, JU, Sasse, A, Klotzsch, C. Intimal flap in a common carotid artery in a patient with Marfan’s syndrome. Ultraschall Med 2006;27:487–488.CrossRefGoogle Scholar
Loeys, BL, Dietz, HC, Braverman, AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010;47:476–485.Google Scholar
Majamaa, K, Moilanen, JS, Uimonen, S, et al. Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes: Prevalence of the mutation in an adult population. Am J Hum Genet 1998;63:447–454.Google Scholar
Testai, FD, Gorelick, PB. Inherited metabolic disorders and stroke part 1: Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Arch Neurol 2010;67:19–24.Google Scholar
Sproule, DM, Kaufmann, P. Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes: Basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci 2008;1142:133–158.Google Scholar
Ito, H, Mori, K, Kagami, S. Neuroimaging of stroke-like episodes in MELAS. Brain Dev 2011;33:283–288.Google Scholar
Yoneda, M, Maeda, M, Kimura, H, Fujii, A, Katayama, K, Kuriyama, M. Vasogenic edema on MELAS: A serial study with diffusion-weighted MR imaging. Neurology 1999;53:2182–2184.Google Scholar
Thambisetty, M, Newman, NJ, Glass, JD, Frankel, MR. A practical approach to the diagnosis and management of MELAS: Case report and review. Neurologist 2002;8:302–312.Google Scholar
Rodriguez, MC, MacDonald, JR, Mahoney, DJ, Parise, G, Beal, MF, Tarnopolsky, MA. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve 2007;35:235–242.Google Scholar
Napolitano, A, Salvetti, S, Vista, M, Lombardi, V, Siciliano, G, Giraldi, C. Long-term treatment with idebenone and riboflavin in a patient with MELAS. Neurol Sci 2000;21:S981–982.Google Scholar
Koga, Y, Povalko, N, Nishioka, J, Katayama, K, Kakimoto, N, Matsuishi, T. MELAS and L-arginine therapy: Pathophysiology of stroke-like episodes. Ann N Y Acad Sci 2010;1201:104–110.Google Scholar
Biffi, A, Greenberg, SM. Cerebral amyloid angiopathy: A systematic review. J Clin Neurol 2011;7:1–9.Google Scholar
De Jonghe, C, Zehr, C, Yager, D, et al. Flemish and Dutch mutations in amyloid beta precursor protein have different effects on amyloid beta secretion. Neurobiol Dis 1998;5:281–286.Google Scholar
Bornebroek, M, De Jonghe, C, Haan, J, et al. Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): Decreased plasma amyloid-beta 42 concentration. Neurobiol Dis 2003;14:619–623.Google Scholar
Palsdottir, A, Snorradottir, AO, Thorsteinsson, L. Hereditary cystatin C amyloid angiopathy: Genetic, clinical, and pathological aspects. Brain Pathol 2006;16:55–59.Google Scholar
Van Nostrand, WE, Melchor, JP, Cho, HS, Greenberg, SM, Rebeck, GW. Pathogenic effects of D23N Iowa mutant amyloid beta-protein. J Biol Chem 2001;276:32860–32866.Google Scholar
Viswanathan, A, Greenberg, SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol 2011;70:871–880.Google Scholar
Greenberg, SM, O’Donnell, HC, Schaefer, PW, Kraft, E. MRI detection of new hemorrhages: Potential marker of progression in cerebral amyloid angiopathy. Neurology 1999;53:1135–1138.Google Scholar
Knudsen, KA, Rosand, J, Karluk, D, Greenberg, SM. Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston criteria. Neurology 2001;56:537–539.Google Scholar
Gould, DB, Phalan, FC, Breedveld, GJ, et al. Mutations in COL4A1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005;308:1167–1171.CrossRefGoogle ScholarPubMed
Vahedi, K, Massin, P, Guichard, JP, et al. Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy. Neurology 2003;60:57–63.Google Scholar
Sibon, I, Coupry, I, Menegon, P, et al. COL4A1 mutation in Axenfeld–Rieger anomaly with leukoencephalopathy and stroke. Ann Neurol 2007;62:177–184.Google Scholar
Plaisier, E, Alamowitch, S, Gribouval, O, et al. Autosomal-dominant familial hematuria with retinal arteriolar tortuosity and contractures: A novel syndrome. Kidney Int 2005;67:2354–2360.Google Scholar
Vahedi, K, Alamowitch, S. Clinical spectrum of type IV collagen (COL4A1) mutations: A novel genetic multisystem disease. Curr Opin Neurol 2011;24:63–68.Google Scholar
Vahedi, K, Boukobza, M, Massin, P, Gould, DB, Tournier-Lasserve, E, Bousser, M-G. Clinical and brain MRI follow-up study of a family with COL4A1 mutation. Neurology 2007;69:1564–1568.Google Scholar
Lanfranconi, S, Markus, HS. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: A systematic review. Stroke 2010;41:e513–518.Google Scholar
Gould, DB, Phalan, FC, van Mil, SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 2006;354:1489–1496.CrossRefGoogle ScholarPubMed
Rauch, F, Glorieux, FH. Osteogenesis imperfecta. Lancet 2004;363:1377–1385.Google Scholar
Prockop, DJ, Kivirikko, KI. Heritable diseases of collagen. N Engl J Med 1984;311:376–386.Google Scholar
Goddeau, RP Jr, Caplan, LR, Alhazzani, AA. Intraparenchymal hemorrhage in a patient with osteogenesis imperfecta and plasminogen activator inhibitor-1 deficiency. Arch Neurol 2010;67:236–238.Google Scholar
Martin, JJ, Hausser, I, Lyrer, P, et al. Familial cervical artery dissections: Clinical, morphologic, and genetic studies. Stroke 2006;37:2924–2929.Google Scholar
Caplan, LR, Gonzales, G, Buonanno, FS. Case 18 – A 35-year old man with neck pain, hoarseness and dysphagia. N Engl J Med 2012;366:2306–2313.Google Scholar
Bak, S, Gaist, D, Sindrup, SH, Skytthe, A, Christensen, K. Genetic liability in stroke: A long-term follow-up study of Danish twins. Stroke 2002;33:769–774.Google Scholar
Kiely, DK, Wolf, PA, Cupples, LA, Beiser, AS, Myers, RH. Familial aggregation of stroke. The Framingham Study. Stroke 1993;24:1366–1371.Google Scholar
Liao, D, Myers, R, Hunt, S, et al. Familial history of stroke and stroke risk. The Family Heart Study. Stroke 1997;28:1908–1912.Google Scholar
Jood, K, Ladenvall, C, Rosengren, A, Blomstrand, C, Jern, C. Family history in ischemic stroke before 70 years of age: The Sahlgrenska Academy Study on Ischemic Stroke. Stroke 2005;36:1383–1387.Google Scholar
Flossmann, E, Schulz, UG, Rothwell, PM. Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke. Stroke 2004;35:212–227.Google Scholar
Jerrard-Dunne, P, Cloud, G, Hassan, A, Markus, HS. Evaluating the genetic component of ischemic stroke subtypes: A family history study. Stroke 2003;34:1364–1369.Google Scholar
Polychronopoulos, P, Gioldasis, G, Ellul, J, et al. Family history of stroke in stroke types and subtypes. J Neurol Sci 2002;195:117–122.Google Scholar
Lee, TH, Hsu, WC, Chen, CJ, Chen, ST. Etiologic study of young ischemic stroke in Taiwan. Stroke 2002;33:1950–1955.Google Scholar
Yang, J, Benyamin, B, McEvoy, BP, et al. Common SNPs explain a large proportion of the heritability for human height. Nat Genet 2010;42:565–569.Google Scholar
Bevan, S, Traylor, M, Adib-Samii, P, et al. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke 2012;43:3161–3167.Google Scholar
Devan, WJ, Falcone, GJ, Anderson, CD, et al. Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage. Stroke 2013;44:1578–1583.Google Scholar
Hassan, A, Markus, HS. Genetics and ischaemic stroke. Brain 2000;123(Pt 9):1784–1812.CrossRefGoogle ScholarPubMed
Zondervan, KT, Cardon, LR. Designing candidate gene and genome-wide case-control association studies. Nat Protoc 2007;2:2492–2501.Google Scholar
Zeggini, E, Scott, LJ, Saxena, R, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008;40:638–645.Google Scholar
Traylor, M, Makela, KM, Kilarski, LL, et al. A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at-onset informed approach. PLoS Genet 2014;10:e1004469.Google Scholar
Traylor, M, Farrall, M, Holliday, EG, et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): A meta-analysis of genome-wide association studies. Lancet Neurol 2012;11:951–962.Google Scholar
Woo, D, Falcone, GJ, Devan, WJ, et al. Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage. Am J Hum Genet 2014;94:511–521.Google Scholar
Bellenguez, C, Bevan, S, Gschwendtner, A, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet 2012;44:328–333.Google Scholar
Holliday, EG, Maguire, JM, Evans, TJ, et al. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nat Genet 2012;44:1147–1151.Google Scholar
Kilarski, LL, Achterberg, S, Devan, WJ, et al. Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12. Neurology 2014;83:678–685.Google Scholar
Ikram, MA, Seshadri, S, Bis, JC, et al. Genomewide association studies of stroke. N Engl J Med 2009;360:1718–1728.Google Scholar
Hirschhorn, JN, Lohmueller, K, Byrne, E, Hirschhorn, K. A comprehensive review of genetic association studies. Genet Med 2002;4:45–61.Google Scholar
Feero, WG, Guttmacher, AE, Collins, FS. Genomic medicine – An updated primer. N Engl J Med 2010;362:2001–2011.Google Scholar
McCarthy, MI, Abecasis, GR, Cardon, LR, et al. Genome-wide association studies for complex traits: Consensus, uncertainty and challenges. Nat Rev Genet 2008;9:356–369.Google Scholar
Biffi, A, Sonni, A, Anderson, CD, et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol 2010;68:934–943.Google Scholar
Holliday, EG, Traylor, M, Malik, R, et al. Genetic overlap between diagnostic subtypes of ischemic stroke. Stroke 2015;46:615–619.Google Scholar
Battey, TW, Valant, V, Kassis, SB, et al. Recommendations from the International Stroke Genetics Consortium, part 2: Biological sample collection and storage. Stroke 2015;46:285–290.Google Scholar
Majersik, JJ, Cole, JW, Golledge, J, et al. Recommendations from the International Stroke Genetics Consortium, part 1: Standardized phenotypic data collection. Stroke 2015;46:279–284.Google Scholar
Psaty, BM, O’Donnell, CJ, Gudnason, V, et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ Cardiovasc Genet 2009;2:273–280.Google Scholar
Gretarsdottir, S, Thorleifsson, G, Manolescu, A, et al. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann Neurol 2008;64:402–409.Google Scholar
Lemmens, R, Buysschaert, I, Geelen, V, et al. The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. Stroke 2010;41:1850–1857.Google Scholar
Gudbjartsson, DF, Holm, H, Gretarsdottir, S, et al. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet 2009;41:876–878.Google Scholar
Deloukas, P, Kanoni, S, Willenborg, C, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2013;45:25–33.Google Scholar
Azghandi, S, Prell, C, van der Laan, SW, et al. Deficiency of the stroke relevant HDAC9 gene attenuates atherosclerosis in accord with allele-specific effects at 7p21.1. Stroke 2015;46:197–202.Google Scholar
Cheng, YC, Cole, JW, Kittner, SJ, Mitchell, BD. Genetics of ischemic stroke in young adults. Circ Cardiovasc Genet 2014;7:383–392.Google Scholar
Gschwendtner, A, Bevan, S, Cole, JW, et al. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol 2009;65:531–539.Google Scholar
Williams, FM, Carter, AM, Hysi, PG, et al. Ischemic stroke is associated with the ABO locus: The EuroCLOT study. Ann Neurol 2013;73:16–31.Google Scholar
McArdle, PF, Kittner, SJ, Ay, H, et al. Agreement between TOAST and CCS ischemic stroke classification: The NINDS SiGN study. Neurology 2014;83:1653–1660.Google Scholar
Wu, L, Shen, Y, Liu, X, et al. The 1425G/A SNP in PRKCH is associated with ischemic stroke and cerebral hemorrhage in a Chinese population. Stroke 2009;40:2973–2976.Google Scholar
Serizawa, M, Nabika, T, Ochiai, Y, et al. Association between PRKCH gene polymorphisms and subcortical silent brain infarction. Atherosclerosis 2008;199:340–345.Google Scholar
Kubo, M, Hata, J, Ninomiya, T, et al. A nonsynonymous SNP in PRKCH (protein kinase Ceta) increases the risk of cerebral infarction. Nat Genet 2007;39:212–217.Google Scholar
International Stroke Genetics Consortium, Wellcome Trust Case-Control Consortium 2. Failure to validate association between 12p13 variants and ischemic stroke. N Engl J Med 2010;362:1547–1550.Google Scholar
Bis, JC, DeStefano, A, Liu, X, et al. Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium. PLoS One 2014;9:e99798.Google Scholar
Debette, S, Kamatani, Y, Metso, TM, et al. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. Nat Genet 2015;47:78–83.CrossRefGoogle ScholarPubMed
Anttila, V, Winsvold, BS, Gormley, P, et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat Genet 2013;45:912–917.Google Scholar
Rannikmae, K, Kalaria, RN, Greenberg, SM, et al. APOE associations with severe CAA-associated vasculopathic changes: Collaborative meta-analysis. J Neurol Neurosurg Psychiatry 2014;85:300–305.Google Scholar
Biffi, A, Anderson, CD, Jagiella, JM, et al. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: A genetic association study. Lancet Neurol 2011;10:702–709.Google Scholar
Rannikmae, K, Davies, G, Thomson, PA, et al. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Neurology 2015;84:918–926.Google Scholar
Weng, YC, Sonni, A, Labelle-Dumais, C, et al. COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann Neurol 2012;71:470–477.Google Scholar
Verhaaren, BF, Debette, S, Bis, JC, et al. Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI. Circ Cardiovasc Genet 2015;8:398–409.Google Scholar
Fornage, M, Debette, S, Bis, JC, et al. Genome-wide association studies of cerebral white matter lesion burden: The CHARGE consortium. Ann Neurol 2011;69:928–939.Google Scholar
Lambert, JC, Ibrahim-Verbaas, CA, Harold, D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 2013;45:1452–1458.Google Scholar
Eichler, EE, Flint, J, Gibson, G, et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 2010;11:446–450.Google Scholar
Panoutsopoulou, K, Tachmazidou, I, Zeggini, E. In search of low-frequency and rare variants affecting complex traits. Hum Mol Genet 2013;22:R16–21.Google Scholar
Kiezun, A, Garimella, K, Do, R, et al. Exome sequencing and the genetic basis of complex traits. Nat Genet 2012;44:623–630.Google Scholar
Sivakumaran, S, Agakov, F, Theodoratou, E, et al. Abundant pleiotropy in human complex diseases and traits. Am J Hum Genet 2011;89:607–618.Google Scholar
Dichgans, M, Malik, R, Konig, IR, et al. Shared genetic susceptibility to ischemic stroke and coronary artery disease: A genome-wide analysis of common variants. Stroke 2014;45:24–36.Google Scholar

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