SCREENING FOR C9ORF72 EXPANSION MUTATION IN SERBIAN PATIENTS WITH EARLY ONSET DEMENTIA

Abstract

Early-onset dementia (EOD) is a neurological syndrome conventionally considered to include patients with disease onset before 65 years of age. It has been shown that hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of both familial and sporadic behavioral variant of frontotemporal lobar degeneration (bvFTLD), amyotrophic lateral sclerosis (ALS) as well as combined syndrome FTLD-motor neuron disease (FTLD-MND). To determine the frequency of C9ORF72 expansion mutation (C9+) in cohort of 117 consecutive EOD patients who attended Neurology Clinic, Clinical Centre of Serbia between april 2012 and april 2014. Sizing PCR across the hexanucleotide repeats was performed using previously published primers. Subsequently, all apparently normal homozygous samples were screened for the C9ORF72 GGGGCC expansion using repeat-primed PCR. Fragment length analysis was performed on an ABI 3500 genetic analyzer and analyzed using ABI GeneMapper v4.1. In our cohort, we identified 4 out of 117 (3,4%) EOD patients with C9ORF72 expansion mutation. All C9+ patients were classified in FTLD disease spectrum group 4/49 (8,2%) where 3 patients fulfilled criteria for FTLDbv and 1 patient had FTLD-MND overlap. None of the C9+ patients fulfilled diagnostic criteria for FTLD language variants, FTD-Progressive supranuclear palsy overlap, dementia with Lewy bodies and Alzheimer's dementia. Our findings are consistent with literature data that around 90% of C9ORF72 repeat expansions are associated with clinical presentation of FTDbv, ALS or combined syndrome FTD-MND.