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 β-amyloid precursor protein (βAPP) 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 βAPP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val → Ile) or a valine to glycine (Val → 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 βAPP 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 DAPP717 Val → Ile and βAPP717 Val → 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 βAPP codon 717 mutated families except mean age of onset.
|Original language||English (US)|
|Number of pages||9|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|State||Published - Mar 13 1995|
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience