DLB and PDD: a role for mutations in dementia and Parkinson disease genes?

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• 作者：Bram Meeus^a ; ^b ; Aline Verstraeten^a ; ^b ; David Crosiers^a ; ^b ; ^c ; Sebastiaan Engelborghs^b ; ^d ; Marleen Van den Broeck^a ; ^b ; Maria Mattheijssens^a ; ^b ; Karin Peeters^a ; ^b ; Ellen Corsmit^a ; ^b ; Ellen Elinck^a ; ^b ; Barbara Pickut^c ; Rik Vandenberghe^e ; Patrick Cras^b ; ^c ; Peter Paul De Deyn^b ; ^d ; Christine Van Broeckhoven^a ; ^b ; Jessie Theuns^a ; ^b ; ^{jessie.theuns@molgen.vib-ua.be}
• 关键词：Dementia with Lewy bodies ; Parkinson disease with dementia ; Mutation analyses
• 刊名：Neurobiology of Aging
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：33
• 期：3
• 页码：629.e5-629.e18
• 全文大小：729 K

文摘

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.