Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

Journal Article · Mon Feb 27 04:00:00 EST 1995 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/ajmg.1320600109· OSTI ID:443796

Mullan, M; Bennett, C; Figueredo, C; Crawford, F ^[1]

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1. Univ. of South Florida, Tampa, FL (United States); and others

Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 443796
• Journal Information: American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 1 Vol. 60; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AGE DEPENDENCE
AMINO ACIDS
BIOLOGICAL MARKERS
DOMINANT MUTATIONS
GENE MUTATIONS
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 14
HUMAN CHROMOSOME 21
NERVOUS SYSTEM DISEASES
PATIENTS
PHENOTYPE
PROTEINS
STATISTICS