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Locus-Specific Mutation Databases for Neurodegenerative Brain Diseases

Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
Human Mutation (Impact Factor: 5.05). 09/2012; 33(9):1340-4. DOI: 10.1002/humu.22117
Source: PubMed

ABSTRACT The Alzheimer disease and frontotemporal dementia (AD&FTLD) and Parkinson disease (PD) Mutation Databases make available curated information of sequence variations in genes causing Mendelian forms of the most common neurodegenerative brain disease AD, frontotemporal lobar degeneration (FTLD), and PD. They are established resources for clinical geneticists, neurologists, and researchers in need of comprehensive, referenced genetic, epidemiologic, clinical, neuropathological, and/or cell biological information of specific gene mutations in these diseases. In addition, the aggregate analysis of all information available in the databases provides unique opportunities to extract mutation characteristics and genotype-phenotype correlations, which would be otherwise unnoticed and unexplored. Such analyses revealed that 61.4% of mutations are private to one single family, while only 5.7% of mutations occur in 10 or more families. The five mutations with most frequent independent observations occur in 21% of AD, 43% of FTLD, and 48% of PD families recorded in the Mutation Databases, respectively. Although these figures are inevitably biased by a publishing policy favoring novel mutations, they probably also reflect the occurrence of multiple rare and few relatively common mutations in the inherited forms of these diseases. Finally, with the exception of the PD genes PARK2 and PINK1, all other genes are associated with more than one clinical diagnosis or characteristics thereof.

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Available from: Christine Van Broeckhoven, Aug 16, 2015
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    • "The mutations are shown with the affected amino acid, the affected APP codon and, if applicable, the amino acid alteration resulting from the mutation. Mutations were found using the Alzheimer Disease and Frontotemporal Dementia Mutation Database ( Cruts et al., 2012 ) and PubMed: 1 ( Lan et al., 2014 ); 2 ( Kaden et al., 2012 ). "
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