Mapping of a disease locus for familial rapidly progressive frontotemporal dementia to chromosome 17q12-21

Authors

  • Susanne Froelich,

    1. Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, Huddinge, Sweden
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  • Hans Basun,

    1. Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, Huddinge, Sweden
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  • Charlotte Forsell,

    1. Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, Huddinge, Sweden
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  • Lena Lilius,

    1. Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, Huddinge, Sweden
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  • Karin Axelman,

    1. Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, Huddinge, Sweden
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  • Athena Andreadis,

    1. The Shriver Center, Waltham, Massachusetts
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  • Lars Lannfelt

    Corresponding author
    1. Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, Huddinge, Sweden
    • Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Section of Geriatric Medicine, KFC, Novum, S-141 86 Huddinge, Sweden.
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Abstract

Familial frontotemporal dementia (FTD) is a complex disorder with lack of distinctive histopathological markers found in other types of dementia. Most of the linkage reports from FTD families map the disease loci to chromosome 17q21-22. However, FTD is genetically heterogeneous, as linkage also has been reported to chromosome 3. In the present study, we investigated the genetics of a Swedish family with an early-onset type of rapidly progressive FTD, associated with muscular rigidity and akinetic movements. Neuropathological features such as severe frontal lobe degeneration, spongy changes, and gliosis were present in affected family members. We here report probable linkage to chromosome 17q12-21 with a maximum two-point lod score of 2.76 at θ = 0 for marker D17S806, and a peak multipoint lod score of 2.86 for the same marker. Linkage to chromosome 3 was excluded, as two-point lod scores of −2.79, and −2.27 at θ = 0.01 for markers D3S1603 and D3S1552, respectively, were obtained. Sequencing of the translated exons of a strong candidate gene in the linked region of chromosome 17, the tau gene, failed to identify any mutations segregating with the disease. Am. J. Med. Genet. 74:380–385, 1997. © 1997 Wiley-Liss, Inc.

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