[P3–113]: MUTATIONAL ANALYSIS OF PRNP IN EARLY ONSET ALZHEIMER's DISEASE IN KOREA

The prion protein (PRNP) gene is associated with prion diseases, whereas variants of the PRNP gene may also explain some cases of Alzheimer disease (AD) in Caucasian populations. To determine the prevalence of the PRNP gene in patients with in Korea, we screened all exons of the PRNP gene in the cohorts of 100 AD cases in the Korean population using next generation sequencing studies. In addition, to measure the adverse effects of mutations on protein structure, in silico predictions and 3D modelling were also performed for all the mutant proteins. We found a pathogenic PRNP mutation, p.M232R, which was discovered in a Korean female early onset AD (EOAD) patient in her 51s. Furthermore, two different PRNP mutations as a risk factor Creutzfeldt-Jakob disease (CJD) including p.M129V and p.E219K were also identified in a total of 14 EOAD patients. To our knowledge, this is the first study to reveal a correlation between the PRNP gene and Korean AD patients in a large cohort. The study reports a pathogenic p.M232R mutation verified with structural prediction in a clinically diagnosed EOAD Korean patient. In addition, although the p.M129V, p.E219K and p.M232R mutations have been reported to cause CJD, findings in our patients suggest that not all patients presenting progressive AD with the mutations have Creutzfeldt–Jakob disease.