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Am J Hum Genet. Nov 1997; 61(5): 1131–1138.
PMCID: PMC1716034

Familial multiple-system tauopathy with presenile dementia is localized to chromosome 17.


An autosomal dominant presenile dementia affecting 39 individuals in a seven-generation, 383-member pedigree has been studied at Indiana University. In the affected members of this family, clinical symptoms occurred early in life, with an average age at onset of 48.8 years. The presenting clinical features include disequilibrium, neck stiffness, dysphagia, and memory loss. As the disease progresses, further cognitive decline, superior-gaze palsy, and dystaxia also are observed. The average duration from onset of symptoms to death is approximately 10 years. Neuropathologic studies of nine affected individuals showed neuronal loss in several areas of the CNS, as well as argentophilic tau-immunopositive inclusions in neurons and in oligodendroglia. A limited genomic screen by use of DNA samples from 28 family members localized the gene for this disorder to a 3-cM region on chromosome 17, between the markers THRA1 and D17S791. The gene for tau also was analyzed, through samples from the family.

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  • Abel KJ, Boehnke M, Prahalad M, Ho P, Flejter WL, Watkins M, VanderStoep J, Chandrasekharappa SC, Collins FS, Glover TW, et al. A radiation hybrid map of the BRCA1 region of chromosome 17q12-q21. Genomics. 1993 Sep;17(3):632–641. [PubMed]
  • Andreadis A, Brown WM, Kosik KS. Structure and novel exons of the human tau gene. Biochemistry. 1992 Nov 3;31(43):10626–10633. [PubMed]
  • Bongcam-Rudloff E, Nistér M, Betsholtz C, Wang JL, Stenman G, Huebner K, Croce CM, Westermark B. Human glial fibrillary acidic protein: complementary DNA cloning, chromosome localization, and messenger RNA expression in human glioma cell lines of various phenotypes. Cancer Res. 1991 Mar 1;51(5):1553–1560. [PubMed]
  • Brown J, Ashworth A, Gydesen S, Sorensen A, Rossor M, Hardy J, Collinge J. Familial non-specific dementia maps to chromosome 3. Hum Mol Genet. 1995 Sep;4(9):1625–1628. [PubMed]
  • Conrad C, Andreadis A, Trojanowski JQ, Dickson DW, Kang D, Chen X, Wiederholt W, Hansen L, Masliah E, Thal LJ, et al. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol. 1997 Feb;41(2):277–281. [PubMed]
  • Ghetti B, Dlouhy SR, Giaccone G, Bugiani O, Frangione B, Farlow MR, Tagliavini F. Gerstmann-Sträussler-Scheinker disease and the Indiana kindred. Brain Pathol. 1995 Jan;5(1):61–75. [PubMed]
  • Ghetti B, Murrell J, Benson MD, Farlow MR. Spectrum of amyloid beta-protein immunoreactivity in hereditary Alzheimer disease with a guanine to thymine missense change at position 1924 of the APP gene. Brain Res. 1992 Jan 31;571(1):133–139. [PubMed]
  • Ghetti B, Piccardo P, Spillantini MG, Ichimiya Y, Porro M, Perini F, Kitamoto T, Tateishi J, Seiler C, Frangione B, et al. Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):744–748. [PMC free article] [PubMed]
  • Goldfarb LG, Brown P, Cervenakova L, Gajdusek DC. Molecular genetic studies of Creutzfeldt-Jakob disease. Mol Neurobiol. 1994 Apr-Jun;8(2-3):89–97. [PubMed]
  • Groen JJ, Endtz LJ. Hereditary Pick's disease: second re-examination of the large family and discussion of other hereditary cases, with particular reference to electroencephalography, a computerized tomography. Brain. 1982 Sep;105(Pt 3):443–459. [PubMed]
  • Heutink P, Stevens M, Rizzu P, Bakker E, Kros JM, Tibben A, Niermeijer MF, van Duijn CM, Oostra BA, van Swieten JC. Hereditary frontotemporal dementia is linked to chromosome 17q21-q22: a genetic and clinicopathological study of three Dutch families. Ann Neurol. 1997 Feb;41(2):150–159. [PubMed]
  • Knops J, Johnson-Wood K, Schenk DB, Sinha S, Lieberburg I, McConlogue L. Isolation of baculovirus-derived secreted and full-length beta-amyloid precursor protein. J Biol Chem. 1991 Apr 15;266(11):7285–7290. [PubMed]
  • Lanska DJ, Currier RD, Cohen M, Gambetti P, Smith EE, Bebin J, Jackson JF, Whitehouse PJ, Markesbery WR. Familial progressive subcortical gliosis. Neurology. 1994 Sep;44(9):1633–1643. [PubMed]
  • Lynch T, Sano M, Marder KS, Bell KL, Foster NL, Defendini RF, Sima AA, Keohane C, Nygaard TG, Fahn S, et al. Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex. Neurology. 1994 Oct;44(10):1878–1884. [PubMed]
  • Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA. Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Brain Res. 1986 Dec;387(3):271–280. [PubMed]
  • Nichols WC, Gregg RE, Brewer HB, Jr, Benson MD. A mutation in apolipoprotein A-I in the Iowa type of familial amyloidotic polyneuropathy. Genomics. 1990 Oct;8(2):318–323. [PubMed]
  • O'Connell JR, Weeks DE. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nat Genet. 1995 Dec;11(4):402–408. [PubMed]
  • Petersen RB, Tabaton M, Chen SG, Monari L, Richardson SL, Lynch T, Manetto V, Lanska DJ, Markesbery WR, Lynches T [corrected to Lynch T], et al. Familial progressive subcortical gliosis: presence of prions and linkage to chromosome 17. Neurology. 1995 Jun;45(6):1062–1067. [PubMed]
  • Schäffer AA, Gupta SK, Shriram K, Cottingham RW., Jr Avoiding recomputation in linkage analysis. Hum Hered. 1994 Jul-Aug;44(4):225–237. [PubMed]
  • Schuler GD, Boguski MS, Stewart EA, Stein LD, Gyapay G, Rice K, White RE, Rodriguez-Tomé P, Aggarwal A, Bajorek E, et al. A gene map of the human genome. Science. 1996 Oct 25;274(5287):540–546. [PubMed]
  • Sima AA, Defendini R, Keohane C, D'Amato C, Foster NL, Parchi P, Gambetti P, Lynch T, Wilhelmsen KC. The neuropathology of chromosome 17-linked dementia. Ann Neurol. 1996 Jun;39(6):734–743. [PubMed]
  • Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MR, Ghetti B. Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4113–4118. [PMC free article] [PubMed]
  • Wijker M, Wszolek ZK, Wolters EC, Rooimans MA, Pals G, Pfeiffer RF, Lynch T, Rodnitzky RL, Wilhelmsen KC, Arwert F. Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21. Hum Mol Genet. 1996 Jan;5(1):151–154. [PubMed]
  • Wilhelmsen KC, Lynch T, Pavlou E, Higgins M, Nygaard TG. Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21-22. Am J Hum Genet. 1994 Dec;55(6):1159–1165. [PMC free article] [PubMed]
  • Wszolek ZK, Pfeiffer RF, Bhatt MH, Schelper RL, Cordes M, Snow BJ, Rodnitzky RL, Wolters EC, Arwert F, Calne DB. Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration. Ann Neurol. 1992 Sep;32(3):312–320. [PubMed]
  • Yamaoka LH, Welsh-Bohmer KA, Hulette CM, Gaskell PC, Jr, Murray M, Rimmler JL, Helms BR, Guerra M, Roses AD, Schmechel DE, et al. Linkage of frontotemporal dementia to chromosome 17: clinical and neuropathological characterization of phenotype. Am J Hum Genet. 1996 Dec;59(6):1306–1312. [PMC free article] [PubMed]

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