PMID- 10533070
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20220408
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 14
IP  - 5
DP  - 1999
TI  - DGGE method for the mutational analysis of the coding and proximal promoter
      regions of the Alzheimer's disease presenilin-1 gene: two novel mutations.
PG  - 433-9
AB  - Many different mutations that cause Alzheimer's disease (AD) have been found in
      the presenilin-1 gene (PSEN1) and are associated with the most aggressive forms
      of the disease. With the aim of screening for PSEN1 genetic variations, we
      developed a method based on denaturing gradient gel electrophoresis (DGGE) that
      allows the mutational analysis of all the coding exons and the proximal promoter 
      of PSEN1 using only four DGGE gels. The analysis by this methodology of a sample 
      of 58 early-onset AD (EOAD) patients nonselected for family history resulted in
      finding four genetic variants within the PSEN1 coding region, two of which are
      novel mutations (M233L and A409T), whereas the other two have been reported
      previously (L282R and E318G). We also found a novel mutation within the PSEN1
      proximal promoter (-280 C-->G) that, interestingly, provokes significant changes 
      in the transcriptional activity of the gene in cell lines of neuronal and
      astrocytic, but not hepatic origin. These data strongly suggest that the region
      around -280 of PSEN1 promoter contains a regulatory element that controls its
      transcription specifically in neural cells.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Aldudo, J
AU  - Aldudo J
AD  - Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa 
      (C.S.I.C.-U.A.M.), Universidad Autonoma de Madrid, Cantoblanco, Madrid, Spain.
FAU - Bullido, M J
AU  - Bullido MJ
FAU - Valdivieso, F
AU  - Valdivieso F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*genetics
MH  - Base Sequence
MH  - Case-Control Studies
MH  - DNA Mutational Analysis/*methods
MH  - DNA Primers/genetics
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Humans
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - *Mutation
MH  - Point Mutation
MH  - Presenilin-1
MH  - *Promoter Regions, Genetic
MH  - Transcription, Genetic
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 - 10.1002/(SICI)1098-1004(199911)14:5<433::AID-HUMU10>3.0.CO;2-K [pii]
AID - 10.1002/(SICI)1098-1004(199911)14:5<433::AID-HUMU10>3.0.CO;2-K [doi]
PST - ppublish
SO  - Hum Mutat. 1999;14(5):433-9. doi:
      10.1002/(SICI)1098-1004(199911)14:5<433::AID-HUMU10>3.0.CO;2-K.