title: A case of possibly pathogenicPSEN2R62C mutation in a patient with probable early-onset Alzheimer's dementia supported by structure prediction.
abstract: A 49-year-old Korean male patient with dementia was diagnosed with probable early-onset Alzheimer's disease (AD). He presented with memory problems, personality changes, and disorientation. His family history of dementia was probably negative, since no family member with dementia was found or mentioned. Mild cortical atrophy was observed upon magnetic resonance imaging analyses of his brain, and the single-photon emission computed tomography analysis revealed hypoperfusion in the frontal, temporal, and limbic lobes. The patient was tested for mutations inAPP,PSEN1,PSEN2,PGRN,MAPT, andPRNPgenes. Genetic analysis revealed R62C mutation inPSEN2gene.PSEN2R62C mutation was previously reported in European populations, including Dutch and Belgian families with AD. Herein, we present the first case report ofPSEN2R62C mutation in Asia. PolyPhen-2 and SIFT software analyses predicted this mutation as "possibly damaging", suggesting its potential involvement with AD. In silico protein structural prediction analyses ofPSEN2R62 and C62 revealed two divergent structures, suggesting that large perturbations of R62C mutation might cause dysfunctions ofPSEN2, which may alter the normal amyloid production.
authors.affiliation: Department of Neurology, Busan Metropolitan Dementia Center, Dong-A University College of Medicine, Busan.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Park
authors.affiliation: Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University.
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: An
authors.affiliation: Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University.
authors.forename: Eva
authors.initials: E
authors.lastname: Bagyinszky
authors.affiliation: Department of Neurology, Seoul National University College of Medicine and Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: SangYun
authors.initials: S
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D001208:Asia; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053766:Presenilin-2 / Q000235:genetics*
chemical_list: D053766:Presenilin-2
keywords: Alzheimer’s disease; MRI; PET; PSEN2 mutation; dementia; presenilin-2