HEREDITARY FRONTOTEMPORAL DEMENTIA IS LINKED TO CHROMOSOME-17Q21-Q22 - A GENETIC AND CLINICOPATHOLOGICAL STUDY OF 3 DUTCH FAMILIES

Hereditary frontotemporal dementia (HFTD) is a rare autosomal dominant form of presenile dementia characterized by behavioral changes and re duced speech. Three multigeneration kindreds with this condition, in t he Netherlands, were investigated for clinicopathological comparison a nd linkage analysis. Frontotemporal atrophy on computed tomographic sc anning and/or magnetic resonance imaging was usually present. Single-p hoton emission computed tomography (SPECT) showed frontal hypoperfusio n in the early phase of the disease. Brain tissue showed moderate to s evere atrophy of frontal and temporal cortex with neuronal loss, glios is, and spongiosis. Pick bodies were lacking in all cases of the 3 fam ilies. The mean age of onset varied significantly between families. We report here evidence for linkage to chromosome 17q21-q22 with a maxim um lod score of 4.70 at Theta = 0.05 with the marker D17S932. Recombin ation analysis positions the gene for HFTD in a region of approximatel y 5 cM between markers D17S946 and D17S791. Three other neurodegenerat ive disorders with a strong clinical and pathological resemblance have recently been mapped to the same chromosomal region, suggesting that a group of clinically related neurodegenerative disorders may originat e from mutations in the same gene.