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

Mike Hutton (), Corinne L. Lendon, Patrizia Rizzu, Matt Baker, Susanne Froelich, Henry Houlden, Stuart Pickering-Brown, Sumi Chakraverty, Adrian Isaacs, Andrew Grover, Jennifer Hackett, Jennifer Adamson, Sarah Lincoln, Dennis Dickson, Peter Davies, Ronald C. Petersen, Martijn Stevens, Esther de Graaff, Erwin Wauters, Jeltje van Baren, Marcel Hillebrand, Marijke Joosse, Jennifer M. Kwon, Petra Nowotny, Lien Kuei Che, Joanne Norton, John C. Morris, Lee A. Reed, John Trojanowski, Hans Basun, Lars Lannfelt, Michael Neystat, Stanley Fahn, Francis Dark, Tony Tannenberg, Peter R. Dodd, Nick Hayward, John B. J. Kwok, Peter R. Schofield, Athena Andreadis, Julie Snowden, David Craufurd, David Neary, Frank Owen, Ben A. Oostra, John Hardy, Alison Goate, John van Swieten, David Mann, Timothy Lynch and Peter Heutink ()
Additional contact information
Mike Hutton: Mayo Clinic Jacksonville
Corinne L. Lendon: Dept of Psychiatry, Washington University School of Medicine
Patrizia Rizzu: Dept of Clinical Genetics, Erasmus University Rotterdam
Matt Baker: Mayo Clinic Jacksonville
Susanne Froelich: Dept of Clinical Genetics, Erasmus University Rotterdam
Henry Houlden: Mayo Clinic Jacksonville
Stuart Pickering-Brown: Divn of Neuroscience, School of Biological Sciences, University of Manchester
Sumi Chakraverty: Dept of Psychiatry, Washington University School of Medicine
Adrian Isaacs: Mayo Clinic Jacksonville
Andrew Grover: Mayo Clinic Jacksonville
Jennifer Hackett: Mayo Clinic Jacksonville
Jennifer Adamson: Mayo Clinic Jacksonville
Sarah Lincoln: Mayo Clinic Jacksonville
Dennis Dickson: Mayo Clinic Jacksonville
Peter Davies: Dept of Pathology, Albert Einstein College of Medicine
Ronald C. Petersen: Mayo Clinic
Martijn Stevens: Dept of Neurology, Erasmus University Rotterdam
Esther de Graaff: Dept of Clinical Genetics, Erasmus University Rotterdam
Erwin Wauters: Dept of Clinical Genetics, Erasmus University Rotterdam
Jeltje van Baren: Dept of Clinical Genetics, Erasmus University Rotterdam
Marcel Hillebrand: Dept of Clinical Genetics, Erasmus University Rotterdam
Marijke Joosse: Dept of Clinical Genetics, Erasmus University Rotterdam
Jennifer M. Kwon: Dept of Neurology, Washington University School of Medicine
Petra Nowotny: Dept of Psychiatry, Washington University School of Medicine
Lien Kuei Che: Dept of Psychiatry, Washington University School of Medicine
Joanne Norton: Dept of Neurology, Washington University School of Medicine
John C. Morris: Dept of Neurology, Washington University School of Medicine
Lee A. Reed: Dept of Pathology and Laboratory Medicine, University of Pennsylvania
John Trojanowski: Dept of Pathology and Laboratory Medicine, University of Pennsylvania
Hans Basun: Section of Geriatric Medicine, Institution of Clinical Neuroscience and Family Medicine, Karolinska Institute
Lars Lannfelt: Section of Geriatric Medicine, Institution of Clinical Neuroscience and Family Medicine, Karolinska Institute
Michael Neystat: Dept of Neurology, Columbia University
Stanley Fahn: Dept of Neurology, Columbia University
Francis Dark: Dept of Psychiatry, Princess Alexandra Hosptial
Tony Tannenberg: Dept of Anatomical Pathology, Mater Misericordiae Hospital
Peter R. Dodd: Dept of Biochemistry, University of Queensland
Nick Hayward: Human Genetics Laboratory, Queensland Institute of Medical Research
John B. J. Kwok: Garvan Institute of Medical Research
Peter R. Schofield: Garvan Institute of Medical Research
Athena Andreadis: Dept of Biomedical Sciences, E.K. Shriver Center
Julie Snowden: Dept of Neurology, Manchester Royal Infirmary
David Craufurd: Dept of Clinical Genetics, St Mary's Hospital
David Neary: Dept of Neurology, Manchester Royal Infirmary
Frank Owen: Divn of Neuroscience, School of Biological Sciences, University of Manchester
Ben A. Oostra: Dept of Clinical Genetics, Erasmus University Rotterdam
John Hardy: Mayo Clinic Jacksonville
Alison Goate: Dept of Psychiatry, Washington University School of Medicine
John van Swieten: Dept of Neurology, Erasmus University Rotterdam
David Mann: Dept of Pathological Sciences, University of Manchester
Timothy Lynch: Dept of Neurology, Columbia University
Peter Heutink: Dept of Clinical Genetics, Erasmus University Rotterdam

Nature, 1998, vol. 393, issue 6686, 702-705

Abstract: Abstract Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)1,2,3,4,5,6,7,8,9, historically termed Pick's disease10. 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 characteristics1,2,3,4,5,6,7,8,12. 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 (ref. 13). 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 (refs 12, 14).

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/31508 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:393:y:1998:i:6686:d:10.1038_31508

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/31508

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().