title: DLB and PDD: a role for mutations in dementia and Parkinson disease genes?
abstract: Based on the substantial overlap in clinical and pathological characteristics of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) with Alzheimer disease (AD) and Parkinson disease (PD) we hypothesized that these disorders might share underlying genetic factors. The contribution of both sequence and copy number variants (CNVs) in known AD and PD genes to the genetic etiology of DLB and PDD however is currently unclear. Therefore, we performed a gene-based mutation analysis of all major AD and PD genes in 99 DLB and 75 PDD patients, including familial and sporadic forms, from Flanders, Belgium. Also, copy number variants in APP, SNCA, and PARK2 were determined. In the AD genes we detected proven pathogenic missense mutations in PSEN1 and PSEN2, and 2 novel missense variants in PSEN2 and MAPT. In the PD genes we identified 1 SNCA duplication, the LRRK2 R1441C founder mutation and 4 novel heterozygous missense variants with unknown pathogenicity. Our results suggest a contribution of established AD and PD genes to the genetic etiology of DLB and PDD though to a limited extent. They do support the hypothesis of a genetic overlap between members of the Lewy body disease spectrum, but additional genes still have to exist.
authors: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
authors: Bram
authors: B
authors: Meeus
authors: Aline
authors: A
authors: Verstraeten
authors: David
authors: D
authors: Crosiers
authors: Sebastiaan
authors: S
authors: Engelborghs
authors: Marleen
authors: M
authors: Van den Broeck
authors: Maria
authors: M
authors: Mattheijssens
authors: Karin
authors: K
authors: Peeters
authors: Ellen
authors: E
authors: Corsmit
authors: Ellen
authors: E
authors: Elinck
authors: Barbara
authors: B
authors: Pickut
authors: Rik
authors: R
authors: Vandenberghe
authors: Patrick
authors: P
authors: Cras
authors: Peter Paul
authors: PP
authors: De Deyn
authors: Christine
authors: C
authors: Van Broeckhoven
authors: Jessie
authors: J
authors: Theuns
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D020961:Lewy Body Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D016564:Amyloid beta-Protein Precursor