Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22
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||Baker, M.;Kwok, J. B.;Kucera, S.;Crook, R.;Farrer, M.;Houlden, H.;Isaacs, A.;Lincoln, S.;Onstead, L.;Hardy, J.;Wittenberg, L.;Dodd, P.;Webb, S.;Hayward, N.;Tannenberg, T.;Andreadis, A.;Hallupp, M.;Schofield, P.;Dark, F.;Hutton, M. :|
|Publisher Name||ANNALS OF NEUROLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9392579|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/1069|