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American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2007 Aug-Sep;22(4):294–299. doi: 10.1177/1533317507302320

Progressive Nonfluent Aphasia Associated With a New Mutation V363I in Tau Gene

David G Munoz 1, Raquel Ros 2, Marta Fatas 3, Felix Bermejo 4, Justo García de Yebenes 5
PMCID: PMC10846119  PMID: 17712160

Abstract

Reported here is a new missense mutation V363I in exon 12 of the microtubule-associated protein tau (MAPT) gene associated with progressive nonfluent aphasia, with onset at the age of 69 years in a woman. Although near mute, she maintained complex activities and had no discernible deficits outside of language until the age of 75 years, when progressive gait and swallowing disturbances appeared. There was a history of late-onset aphasia and apraxia in her father. All of her children were asymptomatic adults, but psycholinguistic abnormalities were detected in those bearing the mutation, consisting of difficulties in comprehension, both reading (symbol discrimination and comprehension of oral spelling) and oral (matching sentences to pictures and comprehension of locative relationships). A mutation-bearing sibling showed no abnormalities at 70 years old, consistent with the limited penetrance expected in late-onset disease. The mutation, corresponding to a highly conserved residue in the fourth tubulin-binding repeat, was not present in 194 normal individuals with the same genetic background.

Keywords: frontotemporal dementia, chromosome 17, late onset, penetrance, psycholinguistics

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Contributor Information

David G. Munoz, Banco de Tejidos para Investigacion Neurologica, dave_munoz@yahoo .com, Hospital 12 de Octubre, St. Michael's Hospital, University of Toronto, Ontario, Canada.

Raquel Ros, Banco de Tejidos para Investigacion Neurologica.

Marta Fatas, Banco de Tejidos para Investigacion Neurologica.

Felix Bermejo, Hospital 12 de Octubre.

Justo García de Yebenes, Banco de Tejidos para Investigacion Neurologica, Hospital Ramon y Cajal, Madrid, Spain.

References

  1. Mesulam MM Primary progressive aphasia. Ann Neurol. 2001. ;49:425-432. [PubMed] [Google Scholar]
  2. McKhann GM, Albert MS, Grossman M., Miller B., Dickson D., Trojanowski JQ Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch Neurol. 2001;58:1803-1809. [DOI] [PubMed] [Google Scholar]
  3. Neary D., Snowden JS, Gustafson L., et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546-1554. [DOI] [PubMed] [Google Scholar]
  4. Kertesz A., McMonagle P., Blair M., Davidson W., Munoz DG The evolution and pathology of frontotemporal dementia. Brain. 2005;128:1996-2005. [DOI] [PubMed] [Google Scholar]
  5. Ghetti B., Hutton ML, Wszolek ZK Frontotemporal dementia and Parkinsonism linked to chromosome 17 associated with tau gene mutations (FTDP-17T). In: Dickson DW, ed. Neurodegeneration: The Molecular Pathology of Dementia of Movement Disorders. Basel, Switzerland: ISN Neuropath Press; 2003. [Google Scholar]
  6. Kirshner HS, Tanridag O., Thurman L., Whetsell WO Jr.Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol. 1987;22:527-532. [DOI] [PubMed] [Google Scholar]
  7. Krefft TA, Graff-Radford NR, Dickson DW, Baker M., Castellani RJ Familial primary progressive aphasia. Alzheimer Dis Assoc Disord. 2003;17:106-112. [DOI] [PubMed] [Google Scholar]
  8. Yancopoulou D., Xuereb JH, Crowther RA, Hodges JR, Spillantini MG Tau and alpha-synuclein inclusions in a case of familial frontotemporal dementia and progressive aphasia. J Neuropathol Exp Neurol. 2005;64:245-253. [DOI] [PubMed] [Google Scholar]
  9. Baker M., Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006; 442:916-919. [DOI] [PubMed] [Google Scholar]
  10. Snowden JS, Pickering-Brown SM, Mackenzie IR, et al. Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia. Brain. 2006;129:2808-2810. [DOI] [PubMed] [Google Scholar]
  11. Chapman SB, Rosenberg RN, Weiner MF, Shobe A. Autosomal dominant progressive syndrome of motor-speech loss without dementia . Neurology. 1997;49:1298-1306. [DOI] [PubMed] [Google Scholar]
  12. Godbolt AK, Beck JA, Collinge J., et al. A presenilin 1 R278I mutation presenting with language impairment . Neurology. 2004;63:1702-1704. [DOI] [PubMed] [Google Scholar]
  13. Poorkaj P., Bird TD, Wijsman E., et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia . Ann Neurol. 1998;43:815-825. [DOI] [PubMed] [Google Scholar]
  14. Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS Neuropsychological Assessment. 4th ed. Oxford, England: Oxford University Press; 2004. [Google Scholar]
  15. Goodglass H., Kaplan E. The Assessment of Aphasia and Related Disorders. Philadelphia, Pa: Lea & Febiger; 1983. [Google Scholar]
  16. Kay J., Lesser R., Coltheaert M. Psycholinguistic assessments of language processing in aphasia (PALPA): an introduction. Aphasiology. 1996;10:159-180. [Google Scholar]
  17. Schwartz MF , Saffran EM, Marin OS The word order problem in agrammatism: I: comprehension. Brain Lang. 1980;10:249-262. [DOI] [PubMed] [Google Scholar]
  18. Bird TD, Nochlin D., Poorkaj P., et al. A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain. 1999;122:741-756. [DOI] [PubMed] [Google Scholar]
  19. van Herpen E., Rosso SM, Serverijnen LA, et al. Variable phenotypic expression and extensive tau pathology in two families with the novel tau mutation L315R . Ann Neurol. 2003;54:573-581. [DOI] [PubMed] [Google Scholar]
  20. Hayashi S., Toyoshima Y., Hasegawa M., et al. Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Ann Neurol. 2002;51:525-530. [DOI] [PubMed] [Google Scholar]
  21. Boeve BF, Tremont-Lukats IW, Waclawik AJ, et al. Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation. Brain. 2005; 128:752-772. [DOI] [PubMed] [Google Scholar]
  22. Janssen JC, Warrington EK, Morris HR, et al. Clinical features of frontotemporal dementia due to the intronic tau 10(+16) mutation. Neurology. 2002;58:1161-1168. [DOI] [PubMed] [Google Scholar]
  23. Neumann M., Mittelbronn M., Simon P., et al. A new family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene: neuropathology and molecular effects . Neuropathol Appl Neurobiol. 2005;31:362-373. [DOI] [PubMed] [Google Scholar]
  24. Pickering-Brown SM, Baker M., Nonaka T., et al. Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene. Brain. 2004; 127:1415-1426. [DOI] [PubMed] [Google Scholar]
  25. Lippa CF, Zhukareva V., Kawarai T., et al. Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation. Ann Neurol. 2000;48:850-858. [PubMed] [Google Scholar]
  26. Neumann M., Diekmann S., Bertsch U., Vanmassenhove B., Bogerts B., Kretzschmar HA Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia. Neurogenetics. 2005. ;6:91-95. [DOI] [PubMed] [Google Scholar]
  27. Spillantini MG, Goedert M. Tau protein pathology in neurodegenerative diseases. Trends Neurosci. 1998;21: 428-433. [DOI] [PubMed] [Google Scholar]

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