title: Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22.
abstract: An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We mapped the disease locus to an approximately 26-cM region of chromosome 17q21-22 with a maximum two-point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP-17 candidate region, were also sequenced. This analysis included the microtubule-associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed.
authors.affiliation: Mayo Clinic Jacksonville, FL 32224, USA.
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.forename: J B
authors.initials: JB
authors.lastname: Kwok
authors.forename: S
authors.initials: S
authors.lastname: Kucera
authors.forename: R
authors.initials: R
authors.lastname: Crook
authors.forename: M
authors.initials: M
authors.lastname: Farrer
authors.forename: H
authors.initials: H
authors.lastname: Houlden
authors.forename: A
authors.initials: A
authors.lastname: Isaacs
authors.forename: S
authors.initials: S
authors.lastname: Lincoln
authors.forename: L
authors.initials: L
authors.lastname: Onstead
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: L
authors.initials: L
authors.lastname: Wittenberg
authors.forename: P
authors.initials: P
authors.lastname: Dodd
authors.forename: S
authors.initials: S
authors.lastname: Webb
authors.forename: N
authors.initials: N
authors.lastname: Hayward
authors.forename: T
authors.initials: T
authors.lastname: Tannenberg
authors.forename: A
authors.initials: A
authors.lastname: Andreadis
authors.forename: M
authors.initials: M
authors.lastname: Hallupp
authors.forename: P
authors.initials: P
authors.lastname: Schofield
authors.forename: F
authors.initials: F
authors.lastname: Dark
authors.forename: M
authors.initials: M
authors.lastname: Hutton
mesh_terms: D000328:Adult; D001315:Australia; D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000150:complications / Q000235:genetics*; D054640:Dual Specificity Phosphatase 3; D005192:Family Health; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology / Q000503:physiopathology*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D013702:Temporal Lobe / Q000201:enzymology / Q000503:physiopathology*; D014404:Tubulin / Q000235:genetics
chemical_list: D014404:Tubulin; C517025:DUSP3 protein, human; D054640:Dual Specificity Phosphatase 3; D017027:Protein Tyrosine Phosphatases