Tau is a candidate gene for chromosome 17 frontotemporal dementia
- 1 June 1998
- journal article
- Published by Wiley in Annals of Neurology
- Vol. 43 (6), 815-825
- https://doi.org/10.1002/ana.410430617
Abstract
Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP‐17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21‐22 in a 2‐ to 4‐centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800‐D17S791 FTDP‐17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP‐17 families revealed nine DNA sequence variants, eight of which were also identified controls and are thus polymorphisms. A ninth variant (Val279Met) was found in one FTDP‐17 family but not in the second FTDP‐17 family. Three lines of evidence indicate that the Val279Met change is an FTDP‐17 causative mutation. First, the mutation site is highly conserved, and normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co‐segregates with the disease in family A. Third, the mutation is not found in normal controls.Keywords
This publication has 39 references indexed in Scilit:
- Familial Multiple-System Tauopathy with Presenile Dementia Is Localized to Chromosome 17American Journal of Human Genetics, 1997
- Genetic evidence for the involvement of τ in progressive supranuclear palsyAnnals of Neurology, 1997
- Hereditary frontotemporal dementia is linked to chromosome 17q21—q22: A genetic and clinicopathological study of three dutch familiesAnnals of Neurology, 1997
- Genomic Structure and Expression of STM2, the Chromosome 1 Familial Alzheimer Disease GeneGenomics, 1996
- The neuropathology of chromosome 17‐linked dementiaAnnals of Neurology, 1996
- Translation is Enhanced After Silent Nucleotide Substitutions in A+T‐Rich Sequences of the Coding Region of CD46 cDNAJBIC Journal of Biological Inorganic Chemistry, 1996
- Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tauThe Journal of cell biology, 1994
- Clinical Picture of Frontal Lobe Degeneration of Non-Alzheimer TypeDementia and Geriatric Cognitive Disorders, 1993
- Tau protein binds to microtubules through a flexible array of distributed weak sites.The Journal of cell biology, 1991
- Frontal lobe degeneration of non-Alzheimer type. I. NeuropathologyArchives of Gerontology and Geriatrics, 1987