A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder.
Brain
; 130(Pt 9): 2277-91, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17681982
ABSTRACT
Dementia with Lewy bodies (DLB) represents the second most frequent type of neurodegenerative dementia in the elderly. Although most patients have sporadic DLB, a limited number of DLB families have been described, suggesting that genetic factors may contribute to DLB pathogenesis. Here, we describe a three-generation Belgian family with prominent dementia and parkinsonism, consistent with a diagnosis of DLB, that was autopsy confirmed for the index patient. In a genome-wide scan and subsequent finemapping of candidate loci we obtained significant linkage to 2q35-q36 (Z = 3.01 at D2S1242). Segregation analysis defined a candidate region of 9.2 Mb between D2S433 and chr2q36.3-8, adjacent to the previously reported PARK11 locus. In addition, haplotype sharing studies in another DLB family of close geographical origin with similar clinical and neuropathological features highlighted the specificity of a 2q35-q36 haplotype harbouring a pathogenic mutation that causes DLB in the Belgian family. So far, extensive sequence analysis of five candidate genes within the 2q35-q36 region has not revealed a disease-causing mutation. Together, our data re-emphasize the genetic heterogeneity of DLB, and strongly support the existence of a gene for familial DLB on 2q35-q36. Once identified this will be the first novel causal gene for DLB and can be expected to open new avenues for biological studies of the disease process.
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Base de dados:
MEDLINE
Assunto principal:
Heterogeneidade Genética
/
Doença por Corpos de Lewy
Tipo de estudo:
Prognostic_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article