Autosomal dominant early onset dementia and leukoencephalopathy in a Japanese family: clinical, neuroimaging and genetic studies

• Published in: Journal of the neurological sciences Vol. 147; no. 1; pp. 55 - 62
• Main Authors: Utatsu, Yasuhiko, Takashima, Hiroshi, Michizono, Kumiko, Kanda, Naoaki, Endou, Kouichi, Mitsuyama, Yoshio, Fujimoto, Toshiro, Nagai, Masahiro, Umehara, Fujio, Higuchi, Itsuro, Arimura, Kimiyoshi, Nakagawa, Masanori, Osame, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 20.03.1997; Elsevier Science
• Subjects: Adult; Age of Onset; Aged; Alzheimer's disease; Atrophy - diagnosis; Atrophy - genetics; Biological and medical sciences; Brain - pathology; Brain Diseases - diagnosis; Brain Diseases - genetics; CADASIL; Chromosome Mapping; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia - diagnosis; Dementia - genetics; Early onset dementia; Gene locus; Genes, Dominant; Genetic Linkage; Hereditary dementia; Humans; Japan; Leukoencephalopathy; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Neurology; Pedigree; Japan; CADASIL; Leukoencephalopathy; Alzheimer's disease; Gene locus; Early onset dementia; Hereditary dementia; Human; Nervous system diseases; Genetic inheritance; Family study; Cardiovascular disease; Nuclear magnetic resonance imaging; Japanese; Cerebral disorder; Genetic disease; Vascular disease; Autosomal character; Central nervous system disease; CADASIL syndrome; Medical imagery; Early; Degenerative disease; Dominant character; Diagnosis; Cerebrovascular disease; Dementia
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(96)05310-5

We report here the results of clinical, neuroimaging and genetic studies of autosomal dominant dementia and leukoencephalopathy in a Japanese family. Twenty-two individuals in this family were examined clinically (17 living, 5 deceased), neuroradiologically and genetically (16 of 17 living members). Ten (5 deceased) of 22 individuals had early onset dementia (age of onset: 45.2 ± 12.1 years on average) and four of them had multiple white matter lesions and brain atrophy on brain MRI without history of brain ischemic attack. Another four individuals had abnormal white matter lesions on brain MRI without dementia. Linkage studies for chromosome 1q31–42, 14q24.3 and 21q21 responsible for Alzheimer's disease, chromosome 19p13.1–13.2 for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and chromosome 3 for familial non-specific dementia suggested no specific haplotypes cosegregated with the disease. Apo E genotypes were E2/2 and E2/3 in this family. Clinical, neuroimaging and genetic studies revealed that the disease in this family was distinguished from known familial dementia. This is the first report of a large Japanese family with autosomal dominant early onset dementia and leukoencephalopathy.