Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Export

@article{citeulike:3914044, abstract = {Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10. The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.}, author = {Hutton, M. and Lendon, C. L. and Rizzu, P. and Baker, M. and Froelich, S. and Houlden, H. and Pickering-Brown, S. and Chakraverty, S. and Isaacs, A. and Grover, A. and Hackett, J. and Adamson, J. and Lincoln, S. and Dickson, D. and Davies, P. and Petersen, R. C. and Stevens, M. and de Graaff, E. and Wauters, E. and van Baren, J. and Hillebrand, M. and Joosse, M. and Kwon, J. M. and Nowotny, P. and Che, L. K. and Norton, J. and Morris, J. C. and Reed, L. A. and Trojanowski, J. and Basun, H. and Lannfelt, L. and Neystat, M. and Fahn, S. and Dark, F. and Tannenberg, T. and Dodd, P. R. and Hayward, N. and Kwok, J. B. and Schofield, P. R. and Andreadis, A. and Snowden, J. and Craufurd, D. and Neary, D. and Owen, F. and Oostra, B. A. and Hardy, J. and Goate, A. and van Swieten, J. and Mann, D. and Lynch, T. and Heutink, P.}, citeulike-article-id = {3914044}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/31508}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/9641683}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=9641683}, day = {18}, doi = {10.1038/31508}, issn = {0028-0836}, journal = {Nature}, keywords = {association, linkage, parkinson, tau\_gene}, month = {June}, number = {6686}, pages = {702--705}, posted-at = {2009-10-30 15:21:30}, priority = {2}, title = {Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.}, url = {http://dx.doi.org/10.1038/31508}, volume = {393}, year = {1998} }

TY - JOUR ID - citeulike:3914044 L3 - citeulike-article-id:3914044 N2 - Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10. The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17. IS - 6686 JF - Nature SN - 0028-0836 EP - 705 TI - Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. VL - 393 SP - 702 KW - association KW - linkage KW - parkinson KW - tau_gene AU - Hutton, M AU - Lendon, CL AU - Rizzu, P AU - Baker, M AU - Froelich, S AU - Houlden, H AU - Pickering-Brown, S AU - Chakraverty, S AU - Isaacs, A AU - Grover, A AU - Hackett, J AU - Adamson, J AU - Lincoln, S AU - Dickson, D AU - Davies, P AU - Petersen, RC AU - Stevens, M AU - de Graaff, E AU - Wauters, E AU - van Baren, J AU - Hillebrand, M AU - Joosse, M AU - Kwon, JM AU - Nowotny, P AU - Che, LK AU - Norton, J AU - Morris, JC AU - Reed, LA AU - Trojanowski, J AU - Basun, H AU - Lannfelt, L AU - Neystat, M AU - Fahn, S AU - Dark, F AU - Tannenberg, T AU - Dodd, PR AU - Hayward, N AU - Kwok, JB AU - Schofield, PR AU - Andreadis, A AU - Snowden, J AU - Craufurd, D AU - Neary, D AU - Owen, F AU - Oostra, BA AU - Hardy, J AU - Goate, A AU - van Swieten, J AU - Mann, D AU - Lynch, T AU - Heutink, P PY - 1998/06/18/ UR - http://dx.doi.org/10.1038/31508 ER -