Genetic factors are important in all forms of dementia, especially in early onset dementia. The frequency of major gene defects in dementia has not been investigated in the Netherlands. Furthermore, whether the recently in a FTD family identified PRKAR1B gene is associated with an Alzheimer's disease (AD) like phenotype, has not been studied. With this study, we aimed to investigate the mutation frequency of the major AD and FTD genes and the PRKAR1B gene in a well-defined Dutch cohort of patients with early onset dementia. Mutation analysis of the genes PSEN1, APP, MAPT, GRN, C9orf72 and PRKAR1B was performed on DNA of 229 patients with the clinical diagnosis AD and 74 patients with the clinical diagnosis FTD below the age of 70 years. PSEN1 and APP mutations were found in, respectively 3.5 and 0.4 % of AD patients, and none in FTD patients. C9orf72 repeat expansions were present in 0.4 % of AD and in 9.9 % of FTD patients, whereas MAPT and GRN mutations both were present in 0.4 % in AD patients, and in 1.4 % resp. 2.7 % in FTD patients. We did not find any pathogenic mutations in the PRKAR1B gene. PSEN1 mutations are the most common genetic cause in Dutch AD patients, whereas MAPT and GRN mutations were found in less than 5 percent. C9orf72 repeat expansions were the most common genetic defect in FTD patients. No pathogenic PRKAR1B mutations were found in the early onset AD and FTD patients of our study.

Alzheimer's disease, Frontotemporal dementia, Gene, Mutation, PRKAR1B
dx.doi.org/10.1007/s00415-014-7456-y, hdl.handle.net/1765/67383
Journal of Neurology: official journal of the European Neurological Society
Department of Neurology

Cohn-Hokke, P.E, Wong, T.H, Rizzu, P, Breedveld, G.J, van der Flier, W.M, Scheltens, P, … Pijnenburg, Y.A.L. (2014). Mutation frequency of PRKAR1B and the major familial dementia genes in a Dutch early onset dementia cohort. Journal of Neurology: official journal of the European Neurological Society. doi:10.1007/s00415-014-7456-y