常染色体優性遺伝を示す皮質下梗塞と白質脳症を伴う脳動脈症 ＣＡＤＡＳＩＬ（原標題は英語）

Abstract

More than 80 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), originated from various communities around the world, have been molecularly identified, but all were white. The occurrence of CADASIL in Orientals is uncertain. We genetically identified two unrelated Japanese family with CADASIL, including 5 affected members through 2 generations. Each affected individuals developed recurrent strokes without risk factors resulted in progressive dementia, pseudobulber palsy, and gait disturbance started after the fifth decade of life. Although affected individuals had no vascular risk factors, they revealed varying degrees narrowing of retinal arteries. Their MRI /CT showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECT imaging, there was severe hypoperfusion of blood flow in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials, within the basal lamina of pericytes in muscular capillaries. A heterozygous Arg133Cys mutation was present in affected individuals, in exon 4 of Notch3 gene, where is the hot spot region for CADASIL mutations in Caucasian families. None of non-affected members nor 50 Japanese normal controls revealed this mutation. Thus, our results confirm that CADASIL is a geographical widespread disorder caused by Notch3 mutation, and GOM may be the specific morphologic hallmark.