PMID- 10534245
OWN - NLM
STAT- MEDLINE
DCOM- 19991103
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 53
IP  - 7
DP  - 1999 Oct 22
TI  - Mutational analysis of the tau gene in progressive supranuclear palsy.
PG  - 1421-4
AB  - OBJECTIVE: To identify genetic mutations in the coding regions and the
      splice-donor sites of the tau gene on chromosome 17q in individuals with
      progressive supranuclear palsy (PSP). BACKGROUND: Several studies provide
      evidence for linkage disequilibrium between a PSP disease gene and allelic
      variants of the tau gene. However, a causative mutation has not been identified. 
      METHODS: We designed a study to search for genetic mutations in 15 coding regions
      of the tau gene including the splice-donor sites in 22 patients with PSP by
      comparing the mobility shifts on single-strand conformation analysis with those
      of age-matched controls. Fragments with altered migration were sequenced directly
      and compared for differences in nucleotide composition. Restriction enzyme
      digests were used to confirm single base-pair substitutions. RESULTS: Significant
      differences in mobility shifts were found in exons 1, 4A, and 8 between affected 
      individuals and age-matched controls. All individuals with PSP had a common
      extended haplotype characterized by a homozygous polymorphism in the 5' splice
      site untranslated region of exon 1, two missense mutations in exon 4A (Asp285Asn,
      Ala289Val), and a nonsense mutation in the 5' splice site of exon 8. CONCLUSIONS:
      This study demonstrates that 22 unrelated progressive supranuclear palsy (PSP)
      patients have four identical sequence variants within the tau gene that are not
      present in 24 age-matched controls. Although the functional significance of these
      results on tau protein expression is unknown, the presence of this
      "susceptibility" haplotype in individuals may place them at risk for developing
      PSP.
FAU - Higgins, J J
AU  - Higgins JJ
AD  - Laboratory of Clinical Neurogenetics, Wadsworth Center, New York State Department
      of Health, Albany 12201-0509, USA. jhiggins@wadsworth.org
FAU - Adler, R L
AU  - Adler RL
FAU - Loveless, J M
AU  - Loveless JM
LA  - eng
SI  - GENBANK/AF027491
SI  - GENBANK/AF047858
SI  - GENBANK/AF047861
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (tau Proteins)
SB  - IM
MH  - Aged
MH  - DNA Mutational Analysis
MH  - Female
MH  - Genetic Variation
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Phenotype
MH  - Polymorphism, Single-Stranded Conformational
MH  - Supranuclear Palsy, Progressive/*genetics
MH  - tau Proteins/*genetics
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1212/wnl.53.7.1421 [doi]
PST - ppublish
SO  - Neurology. 1999 Oct 22;53(7):1421-4. doi: 10.1212/wnl.53.7.1421.