J R Murrell1, A M Hake, K A Quaid, M R Farlow, B Ghetti. 1. Department of Pathology and Laboratory Medicine, 635 Barnhill Dr, Medical Science Bldg A128, Indianapolis, IN 46202, USA. jrmurrel@iupui.edu
Abstract
CONTEXT: Alzheimer disease is the most common form of dementia. Mutations in the genes amyloid precursor protein (APP), presenilin 1(PS1) and presenilin 2(PS2) have been found in early-onset familial forms of Alzheimer disease OBJECTIVE: To determine the cause of dementia in a family with early-onset illness. DESIGN, SETTING, AND PARTICIPANTS: A family with a history of dementia was referred to the Indiana Alzheimer Disease Center, Indianapolis. All the research in this study was done in a university or university hospital. The proband and her 4 siblings took part in the study. The proband, who is still alive, showed symptoms of Alzheimer disease at 38 years of age. Genomic DNA was obtained from blood samples of 5 family members. The APPandPS1genes of the proband were screened for mutations by amplification followed by direct sequencing. RESULTS: Sequence of exon 17 of the APPgene revealed a single nucleotide (guanine to cytosine) substitution in 1 allele, resulting in an amino acid change at codon 717 (valine to leucine). Each of the proband's siblings were tested for this mutation by direct sequencing. Two of the 4 were found to have the mutation; one of whom was recently clinically diagnosed at the age of 36 years. CONCLUSIONS: A novel mutation in the APPgene (V717L) has been found in a family with a history of dementia, beginning in the mid to late 30s. The age of onset in this family is earlier than most of the other families with Alzheimer disease who also have APPmutations. Arch Neurol. 2000.
CONTEXT: Alzheimer disease is the most common form of dementia. Mutations in the genes amyloid precursor protein (APP), presenilin 1(PS1) and presenilin 2(PS2) have been found in early-onset familial forms of Alzheimer disease OBJECTIVE: To determine the cause of dementia in a family with early-onset illness. DESIGN, SETTING, AND PARTICIPANTS: A family with a history of dementia was referred to the Indiana Alzheimer Disease Center, Indianapolis. All the research in this study was done in a university or university hospital. The proband and her 4 siblings took part in the study. The proband, who is still alive, showed symptoms of Alzheimer disease at 38 years of age. Genomic DNA was obtained from blood samples of 5 family members. The APPandPS1genes of the proband were screened for mutations by amplification followed by direct sequencing. RESULTS: Sequence of exon 17 of the APPgene revealed a single nucleotide (guanine to cytosine) substitution in 1 allele, resulting in an amino acid change at codon 717 (valine to leucine). Each of the proband's siblings were tested for this mutation by direct sequencing. Two of the 4 were found to have the mutation; one of whom was recently clinically diagnosed at the age of 36 years. CONCLUSIONS: A novel mutation in the APPgene (V717L) has been found in a family with a history of dementia, beginning in the mid to late 30s. The age of onset in this family is earlier than most of the other families with Alzheimer disease who also have APPmutations. Arch Neurol. 2000.
Authors: Andreas Papassotiropoulos; Michael Fountoulakis; Travis Dunckley; Dietrich A Stephan; Eric M Reiman Journal: J Clin Psychiatry Date: 2006-04 Impact factor: 4.384
Authors: Ulrich Finckh; Christian Kuschel; Maria Anagnostouli; Efstratios Patsouris; George V Pantes; Stylianos Gatzonis; Elisabeth Kapaki; Panagiota Davaki; Katrin Lamszus; Dimitrios Stavrou; Andreas Gal Journal: Neurogenetics Date: 2005-03-18 Impact factor: 2.660