Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has been recently reported as a cause of stroke. It is characterized, in the absence of hypertension, by recurrent subcortical ischaemic strokes, starting in early or midadulthood and leading in some patients to dementia. Magnetic resonance imaging and pathological examination show numerous small subcortical infarcts and a diffuse leukoencephalopathy underlaid by a non–arteriosclerotic, non–amyloid angiopathy. We performed genetic linkage analysis in two unrelated families and assigned the disease locus to chromosome 19q12. Multilocus analysis with the location scores method established the best estimate for the location of the affected gene within a 14 centimorgan interval bracketed by D19S221 and D19S222 loci.
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References
Sacco, R.L. et al. Infarcts of undetermined cause: NINCDS stroke data bank. Ann. Neurol. 125, 382–390 (1989).
Pavlakis, S.G., Philipps, P.C., Di Mauro, S., De Vivo, D.C. & Rowland, L.P. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes: a distinctive clinical syndrome. Ann. Neurol. 16, 481–488 (1984).
Mudd, S.H., Levy, H.L. & Skovby, F. Disorders of sulfuration in The Metabolic Basis of Inherited Diseases Vol. 1, 6 edn (Scriver, C., Beaudet, A.L., Sly, W.S., Valle, D. eds) 693–734 (Me Graw-Hill, New York, 1989).
Tournier-Lasserve, E., Iba-Zizen, M.T., Romero, N. & Bousser, M.G. Autosomal dominant syndrome with stroke-like episodes and leukoencephalopathy. Stroke 22, 1297–1302 (1991).
Baudrimont, M., Dubas, F., Joutel, A., Tournier-Lasserve, E. & Bousser, M.G. Autosomal dominant leukoencephalopathy and subcortical ischemic stroke: a clinicopathological study. Stroke (in the press).
Mas, J.L., Dilouya, A. & de Recondo, J. A familial disorder with subcortical ischemic strokes, dementia and leukoencephalopathy. Neurology 42, 1015–1019 (1992).
Stevens, D.L., Hewlett, R.H. & Brownell, B. Chronic familial vascular encephalopathy. Lancet 2, 1364–1365 (1977).
Sonnninen, V. & Savontaus, M.L. Hereditary multi-infarct dementia. Eur. Neurol. 27, 209–215 (1987).
Sourander, P. & Walinder, J. Hereditary multi-infarct dementia. Acta Neuropathol. 39, 247–254 (1977).
Davous, P. & Fallet-Bianco, C. Démence sous corticale familiale avec leuco-encephalopathie artériopathique. Observation clinicopathologique. Rev. Neurol. (Paris) 5, 376–384 (1991).
Salvi, F. et al. Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan. Ital. J. Neurol. Sci. 13, 135–140 (1992).
Van Broeckoven, C. et al. Amyloid β precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch.). Science 248, 1120–1122 (1990).
Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Multilocus linkage analysis in humans : detection of linkage and estimation of recombination. Am. J. hum. Genet. 37, 482–498 (1985).
Weissenbach, J. et al. A second generation linkage map of the human genome. Nature 359, 794–801, (1992).
Chui, H.C. et al. Criteria for the diagnosis of ischemic vascular dementia proposed by the state of California Alzheimer's disease diagnostic and treatment centers. Neurology 42, 473–480 (1992).
Hachinski, V.C. et al. Cerebral blood flow dementia. Arch. Neurol. 32, 637–637 (1975).
Pericak-Vance, M.A. et al. Linkage studies in familial Alzheimer disease : evidence for chromosome 19 linkage. Am. J. hum. Genet. 48, 1034–1050 (1991).
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Tournier-Lasserve, E., Joutel, A., Melki, J. et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 3, 256–259 (1993). https://doi.org/10.1038/ng0393-256
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DOI: https://doi.org/10.1038/ng0393-256
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