DATABASES OFFICIAL JOURNAL www.hgvs.org Locus-Specific Mutation Databases for Neurodegenerative

ABSTRACT: The Alzheimer disease and frontotemporal dementia (AD&FTLD) and Parkinson disease (PD) Mu-tation 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, neurolo-gists, and researchers in need of comprehensive, refer-enced genetic, epidemiologic, clinical, neuropathological, and/or cell biological information of specific gene muta-tions in these diseases. In addition, the aggregate analy-sis 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 re-vealed 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 indepen-dent observations occur in 21 % ofAD, 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 prob-ably 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. HumMutat 33:1340–1344, 2012. C © 2012Wiley Periodicals, Inc