Rare autosomal copy number variations in early-onset familial Alzheimer's 
disease

Hooli, B. V.; Kovacs-Vajna, Z. M.; Mullin, K.; Blumenthal, M. A.; Mattheisen, M.; Zhang, C.; Lange, C.; Mohapatra, G.; Bertram, L.; Tanzi, R. E.

doi:10.1038/mp.2013.77

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Rare autosomal copy number variations in early-onset familial Alzheimer's disease

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Bertram, L.
Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Hooli, B. V., Kovacs-Vajna, Z. M., Mullin, K., Blumenthal, M. A., Mattheisen, M., Zhang, C., et al. (2014). Rare autosomal copy number variations in early-onset familial Alzheimer's disease. Molecular Psychiatry, 19(6), 676-681. doi:10.1038/mp.2013.77.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0018-DE83-F

Abstract

Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using high-density DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias.Molecular Psychiatry advance online publication, 11 June 2013; doi:10.1038/mp.2013.77.