Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene

Jill R. Murrell, Ann Hake, Kimberly A. Quaid, Martin Farlow, Bernardino Ghetti

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 in 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 APP and PS1 genes of the proband were screened for mutations by amplification followed by direct sequencing. Results: Sequence of exon 17 of the APP gene 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 APP gene (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 APP mutations.

Original languageEnglish
Pages (from-to)885-887
Number of pages3
JournalArchives of Neurology
Volume57
Issue number6
StatePublished - Jun 2000

Fingerprint

Amyloid beta-Protein Precursor
Alzheimer Disease
Mutation
Dementia
Genes
Presenilin-1
Siblings
Presenilin-2
Guanine Nucleotides
Cytosine
Valine
Age of Onset
Codon
Leucine
Gene
Onset
Alzheimer's Disease
Protein
Precursor
Exons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene. / Murrell, Jill R.; Hake, Ann; Quaid, Kimberly A.; Farlow, Martin; Ghetti, Bernardino.

In: Archives of Neurology, Vol. 57, No. 6, 06.2000, p. 885-887.

Research output: Contribution to journalArticle

@article{a6a566130bc84f749951db7b7ecc2f1f,
title = "Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene",
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 in 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 APP and PS1 genes of the proband were screened for mutations by amplification followed by direct sequencing. Results: Sequence of exon 17 of the APP gene 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 APP gene (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 APP mutations.",
author = "Murrell, {Jill R.} and Ann Hake and Quaid, {Kimberly A.} and Martin Farlow and Bernardino Ghetti",
year = "2000",
month = "6",
language = "English",
volume = "57",
pages = "885--887",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "6",

}

TY - JOUR

T1 - Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene

AU - Murrell, Jill R.

AU - Hake, Ann

AU - Quaid, Kimberly A.

AU - Farlow, Martin

AU - Ghetti, Bernardino

PY - 2000/6

Y1 - 2000/6

N2 - 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 in 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 APP and PS1 genes of the proband were screened for mutations by amplification followed by direct sequencing. Results: Sequence of exon 17 of the APP gene 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 APP gene (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 APP mutations.

AB - 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 in 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 APP and PS1 genes of the proband were screened for mutations by amplification followed by direct sequencing. Results: Sequence of exon 17 of the APP gene 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 APP gene (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 APP mutations.

UR - http://www.scopus.com/inward/record.url?scp=0034094214&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034094214&partnerID=8YFLogxK

M3 - Article

C2 - 10867787

AN - SCOPUS:0034094214

VL - 57

SP - 885

EP - 887

JO - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 6

ER -