title: The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida.
abstract: Mutations in the gene encoding the presenilin-1 protein (PSEN1) were first discovered to cause Alzheimer's disease (AD) 20 years ago. Since then more than 200 different pathogenic mutations have been reported, including a p.Gly206Ala founder mutation in the Hispanic population. Here we report mutation analysis of known AD genes in a cohort of 27 early-onset (age of onset ≤65, age of death ≤70) Hispanic patients ascertained in Florida. The PSEN1 p.Gly206Ala mutation was identified in 13 out of 27 patients (48.1%), emphasizing the importance of this specific mutation in the etiology of early-onset AD in this population. One other patient carried the known PSEN1 p.Gly378Val mutation. Genotyping of the PSEN1 p.Gly206Ala and p.Gly378Val mutations in 63 late-onset Hispanic AD patients did not identify additional mutation carriers. All p.Gly206Ala mutation carriers shared rare alleles at two microsatellite markers flanking PSEN1 supporting a common founder. This study confirms the p.Gly206Ala variant as a frequent cause of early onset AD in the Hispanic population and for the first time reports the high frequency of this mutation in Hispanics in Florida.
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ravenscroft
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Cyril
authors.initials: C
authors.lastname: Pottier
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Christopher
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Levitch
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Brown
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center Miami Beach, FL, 32224 USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Barker
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center Miami Beach, FL, 32224 USA.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Duara
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center Miami Beach, FL, 32224 USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Greig-Custo
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center Miami Beach, FL, 32224 USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Betancourt
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center Miami Beach, FL, 32224 USA.
authors.forename: Mara
authors.initials: M
authors.lastname: English
authors.affiliation: McKnight Brain Institute, Miller School of Medicine, University of Miami Miami, FL, 32224 USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neuroscience, Mayo ClinicJacksonville, FL, 32224 USA; Department of Neurology, Mayo ClinicJacksonville, FL, 32224 USA.
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Ertekin-Taner
authors.affiliation: Department of Neurology, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, FL, 32224 USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
keywords: Alzheimer’s disease; Hispanic; diagnosis; early-onset; founder mutation; presenilin 1