Progressive nonfluent aphasia associated with a new mutation V363I in tau gene.
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.
Munoz
David G
DG
Banco de Tejidos para Investigacion Neurologica, Madrid, Spain. dave_munoz@yahoo.com
Ros
Raquel
R
Fatas
Marta
M
Bermejo
Felix
F
de Yebenes
Justo García
JG
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*
C054369:MAPT protein, human; D016875:tau Proteins
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