title: Mutation frequency of PRKAR1B and the major familial dementia genes in a Dutch early onset dementia cohort.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, VU University Medical Centre, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands, p.cohn@vumc.nl.
authors.forename: P E
authors.initials: PE
authors.lastname: Cohn-Hokke
authors.forename: T H
authors.initials: TH
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Rizzu
authors.forename: G
authors.initials: G
authors.lastname: Breedveld
authors.forename: W M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: P
authors.initials: P
authors.lastname: Heutink
authors.forename: E J
authors.initials: EJ
authors.lastname: Meijers-Heijboer
authors.forename: J C
authors.initials: JC
authors.lastname: van Swieten
authors.forename: Y A L
authors.initials: YA
authors.lastname: Pijnenburg
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D015331:Cohort Studies; D054753:Cyclic AMP-Dependent Protein Kinase RIbeta Subunit / Q000235:genetics*; D003704:Dementia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology
chemical_list: D054753:Cyclic AMP-Dependent Protein Kinase RIbeta Subunit; C517766:PRKAR1B protein, human
references.citation: Neurology. 2003 Jan 28;60(2):235-9
references.pmid: 12552037
references.citation: Ann Neurol. 1997 Jun;41(6):809-13
references.pmid: 9189043
references.citation: Nucleic Acids Res. 2010 Sep;38(16):e164
references.pmid: 20601685
references.citation: J Neurol Sci. 2007 Jan 31;252(2):173-6
references.pmid: 17188713
references.citation: Bioinformatics. 2009 Aug 15;25(16):2078-9
references.pmid: 19505943
references.citation: Neurology. 2002 Jun 11;58(11):1615-21
references.pmid: 12058088
references.citation: Alzheimer Dis Assoc Disord. 2010 Jul-Sep;24(3):303-7
references.pmid: 20683187
references.citation: Brain. 2012 Mar;135(Pt 3):723-35
references.pmid: 22300876
references.citation: J Neurol Sci. 1998 Sep 18;160(1):76-81
references.pmid: 9804121
references.citation: Neuron. 2011 Oct 20;72(2):257-68
references.pmid: 21944779
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Brain. 2014 May;137(Pt 5):1361-73
references.pmid: 24722252
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2012 Sep;159B(6):628-43
references.pmid: 22815225
references.citation: Lancet Neurol. 2008 Oct;7(10):965-74
references.pmid: 18771956
references.citation: J Alzheimers Dis. 2011;27(4):781-90
references.pmid: 21891865
references.citation: Genome Res. 2010 Sep;20(9):1297-303
references.pmid: 20644199
references.citation: Neurology. 1998 Dec;51(6):1546-54
references.pmid: 9855500
references.citation: J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1206-9
references.pmid: 12933919
references.citation: Neurology. 2008 Oct 14;71(16):1220-6
references.pmid: 18703462
references.citation: Clin Chem Lab Med. 2007;45(11):1421-34
references.pmid: 17970699
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: J Med Genet. 2014 Jun;51(6):419-24
references.pmid: 24706941
references.citation: Eur J Hum Genet. 2013 Jan;21(1):102-8
references.pmid: 22692064