Genetic testing in familial and young-onset Alzheimer's disease: mutation spectrum in a Serbian cohort

Dobricic, Valerija; Stefanova, Elka; Jankovic, Milena; Gurunlian, Nicole; Novakovic, Ivana; Hardy, John; Kostic, Vladimir; Guerreiro, Rita

doi:10.1016/j.neurobiolaging.2011.12.007

« Previous Next »Neurobiology of Aging
Volume 33, Issue 7 , Pages 1481.e7-1481.e12, July 2012

Genetic testing in familial and young-onset Alzheimer's disease: mutation spectrum in a Serbian cohort

Valerija Dobricic
- Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia
Elka Stefanova
- Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
Milena Jankovic
- School of Medicine, University of Belgrade, Belgrade, Serbia
Nicole Gurunlian
- Reta Lilla Weston Laboratories and Department of Molecular Neuroscience, Institute of Neurology, London, UK
Ivana Novakovic
- Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
John Hardy
- Reta Lilla Weston Laboratories and Department of Molecular Neuroscience, Institute of Neurology, London, UK
Vladimir Kostic
- Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
Rita Guerreiro
- Reta Lilla Weston Laboratories and Department of Molecular Neuroscience, Institute of Neurology, London, UK
- Corresponding author. Tel.: +44 (0)20 3448 3936; fax: +44 (0)207 833 1017

Received 15 September 2011; received in revised form 28 November 2011; accepted 1 December 2011. published online 06 January 2012.

Abstract

Alzheimer's disease (AD) is the most common form of dementia. To date, more than 200 mutations in three genes have been identified as cause of early-onset autosomal dominant inherited AD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in Serbian patients with positive family history of AD or/and early-onset AD. We performed a genetic screening for mutations in the coding regions of Presenilins 1 and 2 (PSEN1 and PSEN2), as well as exons 16 and 17 of the Amyloid Precursor Protein gene (APP) in a total of 47 patients from Serbia with a clinical diagnosis of familial and/or early-onset AD (mean age at onset of 60.3 years; range 32–77). We found one novel mutation in PSEN1, one novel variant in PSEN2, and three previously described variants, one in each of the analyzed genes. Interestingly, we identified one patient harboring two heterozygous mutations: one in APP (p.L723P) and one in PSEN1 (p.R108Q).

Keywords: Alzheimer's disease , Mutations , Serbia , Presenilins , APP