title: Progressive nonfluent aphasia associated with a new mutation V363I in tau gene.
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.
authors: Banco de Tejidos para Investigacion Neurologica, Madrid, Spain. dave_munoz@yahoo.com
authors: David G
authors: DG
authors: Munoz
authors: Raquel
authors: R
authors: Ros
authors: Marta
authors: M
authors: Fatas
authors: Felix
authors: F
authors: Bermejo
authors: Justo García
authors: JG
authors: de Yebenes
mesh_terms: D000328:Adult; D000368:Aged; D018888:Aphasia, Primary Progressive / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D016241:Child of Impaired Parents / Q000706:statistics & numerical data; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D035781:Siblings; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
references: J Neuropathol Exp Neurol. 2005 Mar;64(3):245-53
references: 15804056
references: Brain. 1999 Apr;122 ( Pt 4):741-56
references: 10219785
references: Neurology. 2004 Nov 9;63(9):1702-4
references: 15534260
references: Neuropathol Appl Neurobiol. 2005 Aug;31(4):362-73
references: 16008820
references: Brain Lang. 1980 Jul;10(2):249-62
references: 7407546
references: Neurology. 2002 Apr 23;58(8):1161-8
references: 11971081
references: Ann Neurol. 2000 Dec;48(6):850-8
references: 11117541
references: Neurology. 1997 Nov;49(5):1298-306
references: 9371912
references: Ann Neurol. 1998 Jun;43(6):815-25
references: 9629852
references: Brain. 2005 Apr;128(Pt 4):752-72
references: 15615814
references: Brain. 2004 Jun;127(Pt 6):1415-26
references: 15047590
references: Brain. 2006 Nov;129(Pt 11):3091-102
references: 17003069
references: Trends Neurosci. 1998 Oct;21(10):428-33
references: 9786340
references: Ann Neurol. 1987 Oct;22(4):527-32
references: 3435071
references: Alzheimer Dis Assoc Disord. 2003 Apr-Jun;17(2):106-12
references: 12794388
references: Ann Neurol. 2001 Apr;49(4):425-32
references: 11310619
references: Ann Neurol. 2002 Apr;51(4):525-30
references: 11921059
references: Brain. 2005 Sep;128(Pt 9):1996-2005
references: 16033782
references: Arch Neurol. 2001 Nov;58(11):1803-9
references: 11708987
references: Neurology. 1998 Dec;51(6):1546-54
references: 9855500
references: Ann Neurol. 2003 Nov;54(5):573-81
references: 14595646
references: Nature. 2006 Aug 24;442(7105):916-9
references: 16862116
references: Neurogenetics. 2005 May;6(2):91-5
references: 15765246