Early onset autosomal dominant dementia with ataxia, extrapyramidal features, and epilepsy.

Abstract

OBJECTIVE:

To perform a clinical and molecular study of a large autosomal dominant family with a complex neurologic syndrome that comprises early-onset dementia, extrapyramidal and cerebellar features, and epilepsy.

BACKGROUND:

Early-onset forms of dementia often are caused by genetic factors. Mutations of three different genes-amyloid precursor protein (APP), presenilin 1 (PS-1), presenilin 2 (PS-2)-have been found in early-onset autosomal dominant forms of AD, of the human microtubule associated-protein tau gene (MAPT) in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), of the BRI gene in familial British dementia, of the PI12 gene in familial encephalopathy with neuroserpin inclusion bodies. Linkage to chromosome 3 has been found in familial nonspecific dementia (FND) and linkage to chromosome 20 has been found in Huntington disease (HD)-like neurodegenerative disease. Dementia may be a feature of other neurodegenerative diseases such as HD, dentatorubro-pallidoluysian atrophy (DRPLA), diseases caused by mutations of the prion protein gene (PRNP), spinocerebellar ataxias (SCA), and familial parkinsonism.

METHODS:

A southern Italian family with autosomal dominant dementia-plus was observed. The family includes 57 individuals in 5 generations (14 affected, 7 personally observed). The authors performed linkage analysis to APP, PS-1, PS-2, FTDP-17, BRI, PI12, FND, HD-like, SCA4, SCA5, SCA10, SCA11, SCA13, PARK1, PARK2, PARK3 loci; direct mutation analysis of HD, DRPLA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, and PRNP genes; and sequencing of the PRNP open reading frame.

RESULTS:

Linkage to the examined loci was excluded. All of the direct mutation analyses were negative excluding mutations in the examined genes.

CONCLUSIONS:

This family has a peculiar phenotype and molecular analyses excluded genes known to cause hereditary dementias.

• Authors: A Filla, G De Michele, S Cocozza, A Patrignani, G Volpe, I Castaldo, G Ruggiero, V Bonavita, C Masters, G Casari, A Bruni
• Journal: Neurology (Neurology) Vol. 58 Issue 6 Pg. 922-8 (Mar 26 2002) ISSN: 0028-3878 [Print] United States
• PMID: 11914409 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Aged
• Ataxia (genetics, pathology)
• Basal Ganglia Diseases (genetics, pathology)
• Brain (pathology)
• Chromosome Mapping (methods, statistics & numerical data)
• Dementia (genetics, pathology)
• Epilepsy (genetics, pathology)
• Female
• Genes, Dominant
• Humans
• Lod Score
• Male
• Middle Aged
• Pedigree