PMID- 9641683
OWN - NLM
STAT- MEDLINE
DCOM- 19980701
LR  - 20220409
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 393
IP  - 6686
DP  - 1998 Jun 18
TI  - Association of missense and 5'-splice-site mutations in tau with the inherited 
      dementia FTDP-17.
PG  - 702-5
AB  - 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.
FAU - Hutton, M
AU  - Hutton M
AD  - Mayo Clinic Jacksonville, Florida 32224, USA. hutton.michael@mayo.edu
FAU - Lendon, C L
AU  - Lendon CL
FAU - Rizzu, P
AU  - Rizzu P
FAU - Baker, M
AU  - Baker M
FAU - Froelich, S
AU  - Froelich S
FAU - Houlden, H
AU  - Houlden H
FAU - Pickering-Brown, S
AU  - Pickering-Brown S
FAU - Chakraverty, S
AU  - Chakraverty S
FAU - Isaacs, A
AU  - Isaacs A
FAU - Grover, A
AU  - Grover A
FAU - Hackett, J
AU  - Hackett J
FAU - Adamson, J
AU  - Adamson J
FAU - Lincoln, S
AU  - Lincoln S
FAU - Dickson, D
AU  - Dickson D
FAU - Davies, P
AU  - Davies P
FAU - Petersen, R C
AU  - Petersen RC
FAU - Stevens, M
AU  - Stevens M
FAU - de Graaff, E
AU  - de Graaff E
FAU - Wauters, E
AU  - Wauters E
FAU - van Baren, J
AU  - van Baren J
FAU - Hillebrand, M
AU  - Hillebrand M
FAU - Joosse, M
AU  - Joosse M
FAU - Kwon, J M
AU  - Kwon JM
FAU - Nowotny, P
AU  - Nowotny P
FAU - Che, L K
AU  - Che LK
FAU - Norton, J
AU  - Norton J
FAU - Morris, J C
AU  - Morris JC
FAU - Reed, L A
AU  - Reed LA
FAU - Trojanowski, J
AU  - Trojanowski J
FAU - Basun, H
AU  - Basun H
FAU - Lannfelt, L
AU  - Lannfelt L
FAU - Neystat, M
AU  - Neystat M
FAU - Fahn, S
AU  - Fahn S
FAU - Dark, F
AU  - Dark F
FAU - Tannenberg, T
AU  - Tannenberg T
FAU - Dodd, P R
AU  - Dodd PR
FAU - Hayward, N
AU  - Hayward N
FAU - Kwok, J B
AU  - Kwok JB
FAU - Schofield, P R
AU  - Schofield PR
FAU - Andreadis, A
AU  - Andreadis A
FAU - Snowden, J
AU  - Snowden J
FAU - Craufurd, D
AU  - Craufurd D
FAU - Neary, D
AU  - Neary D
FAU - Owen, F
AU  - Owen F
FAU - Oostra, B A
AU  - Oostra BA
FAU - Hardy, J
AU  - Hardy J
FAU - Goate, A
AU  - Goate A
FAU - van Swieten, J
AU  - van Swieten J
FAU - Mann, D
AU  - Mann D
FAU - Lynch, T
AU  - Lynch T
FAU - Heutink, P
AU  - Heutink P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alternative Splicing
MH  - *Chromosomes, Human, Pair 17
MH  - DNA Mutational Analysis
MH  - Dementia/*genetics
MH  - Exons
MH  - Female
MH  - Humans
MH  - Male
MH  - *Mutation
MH  - Nerve Degeneration/genetics
MH  - Pedigree
MH  - RNA Splicing/*genetics
MH  - tau Proteins/*genetics
EDAT- 1998/06/26 02:04
MHDA- 2001/03/23 10:01
CRDT- 1998/06/26 02:04
PHST- 1998/06/26 02:04 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1998/06/26 02:04 [entrez]
AID - 10.1038/31508 [doi]
PST - ppublish
SO  - Nature. 1998 Jun 18;393(6686):702-5. doi: 10.1038/31508.